This document discusses protein structural bioinformatics and methods for predicting protein structure using bioinformatics approaches. It defines protein structural bioinformatics as focusing on representing, storing, analyzing and displaying protein structural information at the atomic scale. It describes how bioinformatics can be used to visualize, align, classify and predict protein structures. It also summarizes several specific methods for predicting protein secondary structure and tertiary structure, including homology modeling, threading and ab initio prediction.
This document summarizes different computational methods for protein structure prediction, including homology modeling, fold recognition, threading, and ab initio modeling. Homology modeling relies on identifying proteins with similar sequences and known structures. Fold recognition and threading can be used when there are no homologs, to identify proteins with the same overall fold but different sequences. Ab initio modeling uses physics-based modeling and protein fragments to predict structure from sequence alone, and has challenges due to the vast number of possible conformations.
This document discusses protein structure prediction. It begins by defining protein structure prediction as inferring a protein's three-dimensional structure from its amino acid sequence. It then outlines different levels of protein structure and some key methods for protein structure prediction, including experimental methods like X-ray crystallography and NMR, as well as computational methods like homology modeling, threading, and ab initio modeling. Specific techniques within these categories like homology modeling steps are also summarized.
Protein threading is a protein structure prediction method that involves "threading" or placing an amino acid sequence into known protein structure templates to find the best matching fold. The key steps are:
1) A query sequence is threaded into structural positions of templates from a structure library to find sequence-structure alignments
2) Alignments are scored and optimized using an objective function accounting for residue interactions and preferences
3) The highest scoring template is selected as the predicted structure, though loop regions are often not accurately predicted
Secondary structure prediction tools analyze a protein's amino acid sequence to predict its 3D structure and function. These tools use various methods like Chou-Fasman, GOR, neural networks, and hidden Markov models to identify alpha helices and beta sheets based on characteristics like residue propensity values, sequence homology, and patterns in windows of amino acids. Accurate prediction of secondary structure is important for determining a protein's tertiary structure and biological role.
The document discusses various computational methods for predicting the three-dimensional structure of proteins from their amino acid sequences. It describes homology modeling, which predicts structures based on known protein structural templates that share sequence homology. It also covers threading/fold recognition and ab initio modeling, which predict structures without templates by using physicochemical principles or energy minimization approaches. Key steps and programs used in each method are outlined.
The SCOP database classifies protein structures hierarchically and describes evolutionary relationships between proteins. It was created in 1994 at the Centre for Protein Engineering and is maintained manually. SCOP links to the Protein Data Bank to obtain structural classifications for each protein structure directly and can also be searched to find a protein's structural class, fold, and domain information.
This document discusses protein threading modeling methods. Protein threading, also called fold recognition, is used to model proteins that have the same fold as proteins with known structures but no homologous sequences. It differs from homology modeling which is used for proteins that have homologous sequences. Protein threading works by using statistical knowledge of relationships between structures in the Protein Data Bank and the sequence of the protein being modeled. It is based on observations that there are a limited number of folds in nature and most new structures have similar folds to ones already in the PDB. The document then describes the general steps of the protein threading method.
The Protein Data Bank (PDB) is an open database that archives 3D structural data of biological macromolecules. It was established in 1971 and currently holds over 150,000 structures determined by X-ray crystallography or NMR spectroscopy. The PDB is overseen by the Worldwide Protein Data Bank and freely accessible online. It serves as a key resource for structural biology and many other databases rely on protein structures deposited in the PDB.
This document summarizes different computational methods for protein structure prediction, including homology modeling, fold recognition, threading, and ab initio modeling. Homology modeling relies on identifying proteins with similar sequences and known structures. Fold recognition and threading can be used when there are no homologs, to identify proteins with the same overall fold but different sequences. Ab initio modeling uses physics-based modeling and protein fragments to predict structure from sequence alone, and has challenges due to the vast number of possible conformations.
This document discusses protein structure prediction. It begins by defining protein structure prediction as inferring a protein's three-dimensional structure from its amino acid sequence. It then outlines different levels of protein structure and some key methods for protein structure prediction, including experimental methods like X-ray crystallography and NMR, as well as computational methods like homology modeling, threading, and ab initio modeling. Specific techniques within these categories like homology modeling steps are also summarized.
Protein threading is a protein structure prediction method that involves "threading" or placing an amino acid sequence into known protein structure templates to find the best matching fold. The key steps are:
1) A query sequence is threaded into structural positions of templates from a structure library to find sequence-structure alignments
2) Alignments are scored and optimized using an objective function accounting for residue interactions and preferences
3) The highest scoring template is selected as the predicted structure, though loop regions are often not accurately predicted
Secondary structure prediction tools analyze a protein's amino acid sequence to predict its 3D structure and function. These tools use various methods like Chou-Fasman, GOR, neural networks, and hidden Markov models to identify alpha helices and beta sheets based on characteristics like residue propensity values, sequence homology, and patterns in windows of amino acids. Accurate prediction of secondary structure is important for determining a protein's tertiary structure and biological role.
The document discusses various computational methods for predicting the three-dimensional structure of proteins from their amino acid sequences. It describes homology modeling, which predicts structures based on known protein structural templates that share sequence homology. It also covers threading/fold recognition and ab initio modeling, which predict structures without templates by using physicochemical principles or energy minimization approaches. Key steps and programs used in each method are outlined.
The SCOP database classifies protein structures hierarchically and describes evolutionary relationships between proteins. It was created in 1994 at the Centre for Protein Engineering and is maintained manually. SCOP links to the Protein Data Bank to obtain structural classifications for each protein structure directly and can also be searched to find a protein's structural class, fold, and domain information.
This document discusses protein threading modeling methods. Protein threading, also called fold recognition, is used to model proteins that have the same fold as proteins with known structures but no homologous sequences. It differs from homology modeling which is used for proteins that have homologous sequences. Protein threading works by using statistical knowledge of relationships between structures in the Protein Data Bank and the sequence of the protein being modeled. It is based on observations that there are a limited number of folds in nature and most new structures have similar folds to ones already in the PDB. The document then describes the general steps of the protein threading method.
The Protein Data Bank (PDB) is an open database that archives 3D structural data of biological macromolecules. It was established in 1971 and currently holds over 150,000 structures determined by X-ray crystallography or NMR spectroscopy. The PDB is overseen by the Worldwide Protein Data Bank and freely accessible online. It serves as a key resource for structural biology and many other databases rely on protein structures deposited in the PDB.
UniProt is a comprehensive, freely accessible database that is a central repository for protein data. It is produced through collaboration between the European Bioinformatics Institute, Swiss Institute of Bioinformatics, and Protein Information Resource. UniProt contains protein sequences, functional information, evolutionary data, and details about biological processes, post-translational modifications, interactions, and subcellular locations to characterize proteins.
The document describes EXPASY (Expert Protein Analysis System), a web server that provides access to databases and analytical tools for proteins and proteomics. It contains Swiss-Prot, Trembl, Swiss-2DPAGE, Prosite, Enzyme, and Swiss-Model Repository databases. Analysis tools are available for tasks like similarity searches, pattern recognition, structure prediction, and sequence alignment. EXPASY was created in 1993 as one of the first biological web servers and has since been expanded and maintained by the SIB Swiss Institute of Bioinformatics.
Homology modeling is a computational method to predict the 3D structure of a protein based on the known structure of homologous proteins. It involves 7 main steps: 1) selecting a template protein with high sequence similarity, 2) aligning the sequences, 3) building the protein backbone, 4) modeling loops and insertions/deletions, 5) refining side chains, 6) refining the overall structure using energy minimization, and 7) evaluating the model. Homology models can accurately predict protein structure when the sequence identity between the target and template is above 30%. Models are useful for studying protein function and designing drugs.
The document discusses protein-protein interactions (PPIs) and methods used to study them. It defines PPIs as physical contacts between two or more proteins through biochemical or electrostatic forces. It describes different types of PPIs including homo-oligomers, hetero-oligomers, covalent and non-covalent interactions. Common methods to study PPIs are also summarized, such as yeast two-hybrid systems, co-immunoprecipitation, and protein interaction databases. The applications and importance of PPI research are mentioned including roles in various cellular processes and diseases.
INTRODUCTION
STRUCTURAL PROTEOMICS
WHAT IS THE IMPORTANCE OF STUDY OF PROTEIN
METHODS FOR SOLVING PROTEIN STRUCTURE
1. X- RAY CRYSTALLOGRAPHY
INTRODUCTION
PROCEDURE
LIMITATIONS
2.NUCLEAR MAGNETIC RESONANCE
PROTEIN STRUCTURE DETERMINATION
3. MASS SPECTROMETER
MALDI
ESI
STRUCTURE MODELING
APPLICATIONS
CONCLUSION
REFERENCES
The document discusses Prosite, a database of protein family signatures that can be used to determine the function of uncharacterized proteins. It contains patterns and profiles formulated to identify which known protein family a new sequence belongs to. The Prosite database consists of two files - a data file containing information for scanning sequences, and a documentation file describing each pattern and profile. New Prosite entries are mainly profiles developed by collaborators at the SIB Swiss Institute of Bioinformatics to identify distantly related proteins based on conserved residues.
The CATH database hierarchically classifies protein domains obtained from protein structures deposited in the Protein Data Bank. Domain identification and classification uses both manual and automated procedures. CATH includes domains from structures determined at 4 angstrom resolution or better that are at least 40 residues long with 70% or more residues having defined side chains. Submitted protein chains are divided into domains, which are then classified in CATH.
Secondary Structure Prediction of proteins Vijay Hemmadi
Secondary structure prediction has been around for almost a quarter of a century. The early methods suffered from a lack of data. Predictions were performed on single sequences rather than families of homologous sequences, and there were relatively few known 3D structures from which to derive parameters. Probably the most famous early methods are those of Chou & Fasman, Garnier, Osguthorbe & Robson (GOR) and Lim. Although the authors originally claimed quite high accuracies (70-80 %), under careful examination, the methods were shown to be only between 56 and 60% accurate (see Kabsch & Sander, 1984 given below). An early problem in secondary structure prediction had been the inclusion of structures used to derive parameters in the set of structures used to assess the accuracy of the method.
Some good references on the subject:
The document discusses experimental and computational methods for protein structure prediction. Experimental methods like NMR, X-ray crystallography, and cryo-EM can accurately determine protein structure but require isolating and crystallizing the protein. Computational methods like homology modeling, ab initio modeling, and threading/folding predict structure from sequence alone and are less accurate but do not require crystallization. Computational methods work best when a template structure is available from experimental data. While experimental methods are very accurate, they are also costly and difficult for large numbers of proteins, making computational methods a useful complement despite being less accurate.
The document discusses various methods for structurally aligning proteins, including combinatorial extension, VAST, DALI, SSAP, and TM-align. It also describes Ramachandran plots, which show allowed and favored phi/psi dihedral angle combinations for protein backbone chains based on steric constraints. Structural alignment methods are useful for detecting evolutionary relationships between proteins with low sequence similarity. Ramachandran plots help validate protein structures by identifying conformations not allowed by steric hindrance.
The experimental methods used by biotechnologists to determine the structures of proteins demand sophisticated equipment and time.
A host of computational methods are developed to predict the location of secondary structure elements in proteins for complementing or creating insights into experimental results.
Chou-Fasman algorithm is an empirical algorithm developed for the prediction of protein secondary structure
Ab initio protein structure prediction uses computational methods to predict a protein's 3D structure from its amino acid sequence. It relies on conformational searching to generate structure decoys and selecting native-like models. The key factors for success are an accurate energy function, efficient search methods like molecular dynamics or genetic algorithms, and effective selection of models close to the native structure. Model selection approaches include energy evaluations, compatibility scores, clustering of similar decoys, and identifying the lowest energy conformations.
Protein Sequence, Structure, and Functional Databases: UniProtKB, Swiss-Prot, TrEMBL, PIR, MIPS, PROSITE, PRINTS, BLOCKS, Pfam, NDRB, OWL, PDB, SCOP, CATH, NDB, PQS, SYSTERS, and Motif. Presented at UGC Sponsored National Workshop on Bioinformatics and Sequence Analysis conducted by Nesamony Memorial Christian College, Marthandam on 9th and 10th October, 2017 by Prof. T. Ashok Kumar
Prediction of the three dimensional structure of a given protein sequence i.e. target protein from the amino acid sequence of a homologous (template) protein for which an X-ray or NMR structure is available based on an alignment to one or more known protein structures
Homology modeling is a technique used to predict the 3D structure of a protein based on the alignment of its amino acid sequence to known protein structures. It relies on the observation that structure is more conserved than sequence during evolution. The key steps in homology modeling include: 1) identifying a template structure through sequence alignment tools like BLAST, 2) correcting any errors in the initial alignment, 3) generating the protein backbone based on the template structure, 4) modeling any loops or missing regions, 5) adding side chains, 6) optimizing the model structure energetically, and 7) validating that the final model matches the template structure and has correct stereochemistry. Homology modeling is useful for applications like structure-based drug design
The EcoCyc database is a freely accessible, comprehensive database that combines information about the genome and metabolism of Escherichia coli K-12. It describes the known genes of E. coli, the enzymes encoded by these genes, and how these enzymes catalyze reactions organized into metabolic pathways. The EcoCyc database is jointly developed and curated by researchers at SRI International and the Marine Biological Laboratory based on experimental literature. It provides graphical tools for visualizing and exploring genomic and biochemical data through its user interface, facilitating analysis of high-throughput data and metabolic modeling.
This document outlines the course content for a bioinformatics course covering 4 units:
Unit 1 introduces basic concepts of bioinformatics including proteins, DNA, RNA, and sequence, structure, and function.
Unit 2 covers major bioinformatics databases including those for nucleotide sequences, protein sequences, sequence motifs, protein structures, and other relevant databases.
Unit 3 discusses topics like single and pairwise sequence alignment, scoring matrices, and multiple sequence alignments.
Unit 4 covers the human genome project, gene and genomic databases, genomic data mining, and microarray techniques.
The document discusses several protein sequence databases including Swiss-Prot, GenPept/TREMBL, PIR, PDB, and MMDB. It provides details on Swiss-Prot, describing it as a manually curated database that distinguishes itself from others through annotations, minimal redundancy, and integration with other databases. The annotations in Swiss-Prot include core data as well as additional details on the protein's function, modifications, domains, structure, and relationships to other proteins and diseases.
The document discusses protein structure prediction. It begins by reviewing protein structure, including primary, secondary, tertiary, and quaternary structure. It then describes the building blocks of proteins, amino acids, and how their properties allow formation of regular secondary structures like alpha helices and beta sheets. The document outlines different types of secondary structure and how their patterns of hydrogen bonding influence 3D structure. It concludes by describing six classes of protein structure defined by their arrangements of alpha helices and beta sheets.
protein structure prediction methods. homology modelling, fold recognition, threading, ab initio methods. in short and easy form slides. after one time read you can easily understand methods for protein structure prediction.
UniProt is a comprehensive, freely accessible database that is a central repository for protein data. It is produced through collaboration between the European Bioinformatics Institute, Swiss Institute of Bioinformatics, and Protein Information Resource. UniProt contains protein sequences, functional information, evolutionary data, and details about biological processes, post-translational modifications, interactions, and subcellular locations to characterize proteins.
The document describes EXPASY (Expert Protein Analysis System), a web server that provides access to databases and analytical tools for proteins and proteomics. It contains Swiss-Prot, Trembl, Swiss-2DPAGE, Prosite, Enzyme, and Swiss-Model Repository databases. Analysis tools are available for tasks like similarity searches, pattern recognition, structure prediction, and sequence alignment. EXPASY was created in 1993 as one of the first biological web servers and has since been expanded and maintained by the SIB Swiss Institute of Bioinformatics.
Homology modeling is a computational method to predict the 3D structure of a protein based on the known structure of homologous proteins. It involves 7 main steps: 1) selecting a template protein with high sequence similarity, 2) aligning the sequences, 3) building the protein backbone, 4) modeling loops and insertions/deletions, 5) refining side chains, 6) refining the overall structure using energy minimization, and 7) evaluating the model. Homology models can accurately predict protein structure when the sequence identity between the target and template is above 30%. Models are useful for studying protein function and designing drugs.
The document discusses protein-protein interactions (PPIs) and methods used to study them. It defines PPIs as physical contacts between two or more proteins through biochemical or electrostatic forces. It describes different types of PPIs including homo-oligomers, hetero-oligomers, covalent and non-covalent interactions. Common methods to study PPIs are also summarized, such as yeast two-hybrid systems, co-immunoprecipitation, and protein interaction databases. The applications and importance of PPI research are mentioned including roles in various cellular processes and diseases.
INTRODUCTION
STRUCTURAL PROTEOMICS
WHAT IS THE IMPORTANCE OF STUDY OF PROTEIN
METHODS FOR SOLVING PROTEIN STRUCTURE
1. X- RAY CRYSTALLOGRAPHY
INTRODUCTION
PROCEDURE
LIMITATIONS
2.NUCLEAR MAGNETIC RESONANCE
PROTEIN STRUCTURE DETERMINATION
3. MASS SPECTROMETER
MALDI
ESI
STRUCTURE MODELING
APPLICATIONS
CONCLUSION
REFERENCES
The document discusses Prosite, a database of protein family signatures that can be used to determine the function of uncharacterized proteins. It contains patterns and profiles formulated to identify which known protein family a new sequence belongs to. The Prosite database consists of two files - a data file containing information for scanning sequences, and a documentation file describing each pattern and profile. New Prosite entries are mainly profiles developed by collaborators at the SIB Swiss Institute of Bioinformatics to identify distantly related proteins based on conserved residues.
The CATH database hierarchically classifies protein domains obtained from protein structures deposited in the Protein Data Bank. Domain identification and classification uses both manual and automated procedures. CATH includes domains from structures determined at 4 angstrom resolution or better that are at least 40 residues long with 70% or more residues having defined side chains. Submitted protein chains are divided into domains, which are then classified in CATH.
Secondary Structure Prediction of proteins Vijay Hemmadi
Secondary structure prediction has been around for almost a quarter of a century. The early methods suffered from a lack of data. Predictions were performed on single sequences rather than families of homologous sequences, and there were relatively few known 3D structures from which to derive parameters. Probably the most famous early methods are those of Chou & Fasman, Garnier, Osguthorbe & Robson (GOR) and Lim. Although the authors originally claimed quite high accuracies (70-80 %), under careful examination, the methods were shown to be only between 56 and 60% accurate (see Kabsch & Sander, 1984 given below). An early problem in secondary structure prediction had been the inclusion of structures used to derive parameters in the set of structures used to assess the accuracy of the method.
Some good references on the subject:
The document discusses experimental and computational methods for protein structure prediction. Experimental methods like NMR, X-ray crystallography, and cryo-EM can accurately determine protein structure but require isolating and crystallizing the protein. Computational methods like homology modeling, ab initio modeling, and threading/folding predict structure from sequence alone and are less accurate but do not require crystallization. Computational methods work best when a template structure is available from experimental data. While experimental methods are very accurate, they are also costly and difficult for large numbers of proteins, making computational methods a useful complement despite being less accurate.
The document discusses various methods for structurally aligning proteins, including combinatorial extension, VAST, DALI, SSAP, and TM-align. It also describes Ramachandran plots, which show allowed and favored phi/psi dihedral angle combinations for protein backbone chains based on steric constraints. Structural alignment methods are useful for detecting evolutionary relationships between proteins with low sequence similarity. Ramachandran plots help validate protein structures by identifying conformations not allowed by steric hindrance.
The experimental methods used by biotechnologists to determine the structures of proteins demand sophisticated equipment and time.
A host of computational methods are developed to predict the location of secondary structure elements in proteins for complementing or creating insights into experimental results.
Chou-Fasman algorithm is an empirical algorithm developed for the prediction of protein secondary structure
Ab initio protein structure prediction uses computational methods to predict a protein's 3D structure from its amino acid sequence. It relies on conformational searching to generate structure decoys and selecting native-like models. The key factors for success are an accurate energy function, efficient search methods like molecular dynamics or genetic algorithms, and effective selection of models close to the native structure. Model selection approaches include energy evaluations, compatibility scores, clustering of similar decoys, and identifying the lowest energy conformations.
Protein Sequence, Structure, and Functional Databases: UniProtKB, Swiss-Prot, TrEMBL, PIR, MIPS, PROSITE, PRINTS, BLOCKS, Pfam, NDRB, OWL, PDB, SCOP, CATH, NDB, PQS, SYSTERS, and Motif. Presented at UGC Sponsored National Workshop on Bioinformatics and Sequence Analysis conducted by Nesamony Memorial Christian College, Marthandam on 9th and 10th October, 2017 by Prof. T. Ashok Kumar
Prediction of the three dimensional structure of a given protein sequence i.e. target protein from the amino acid sequence of a homologous (template) protein for which an X-ray or NMR structure is available based on an alignment to one or more known protein structures
Homology modeling is a technique used to predict the 3D structure of a protein based on the alignment of its amino acid sequence to known protein structures. It relies on the observation that structure is more conserved than sequence during evolution. The key steps in homology modeling include: 1) identifying a template structure through sequence alignment tools like BLAST, 2) correcting any errors in the initial alignment, 3) generating the protein backbone based on the template structure, 4) modeling any loops or missing regions, 5) adding side chains, 6) optimizing the model structure energetically, and 7) validating that the final model matches the template structure and has correct stereochemistry. Homology modeling is useful for applications like structure-based drug design
The EcoCyc database is a freely accessible, comprehensive database that combines information about the genome and metabolism of Escherichia coli K-12. It describes the known genes of E. coli, the enzymes encoded by these genes, and how these enzymes catalyze reactions organized into metabolic pathways. The EcoCyc database is jointly developed and curated by researchers at SRI International and the Marine Biological Laboratory based on experimental literature. It provides graphical tools for visualizing and exploring genomic and biochemical data through its user interface, facilitating analysis of high-throughput data and metabolic modeling.
This document outlines the course content for a bioinformatics course covering 4 units:
Unit 1 introduces basic concepts of bioinformatics including proteins, DNA, RNA, and sequence, structure, and function.
Unit 2 covers major bioinformatics databases including those for nucleotide sequences, protein sequences, sequence motifs, protein structures, and other relevant databases.
Unit 3 discusses topics like single and pairwise sequence alignment, scoring matrices, and multiple sequence alignments.
Unit 4 covers the human genome project, gene and genomic databases, genomic data mining, and microarray techniques.
The document discusses several protein sequence databases including Swiss-Prot, GenPept/TREMBL, PIR, PDB, and MMDB. It provides details on Swiss-Prot, describing it as a manually curated database that distinguishes itself from others through annotations, minimal redundancy, and integration with other databases. The annotations in Swiss-Prot include core data as well as additional details on the protein's function, modifications, domains, structure, and relationships to other proteins and diseases.
The document discusses protein structure prediction. It begins by reviewing protein structure, including primary, secondary, tertiary, and quaternary structure. It then describes the building blocks of proteins, amino acids, and how their properties allow formation of regular secondary structures like alpha helices and beta sheets. The document outlines different types of secondary structure and how their patterns of hydrogen bonding influence 3D structure. It concludes by describing six classes of protein structure defined by their arrangements of alpha helices and beta sheets.
protein structure prediction methods. homology modelling, fold recognition, threading, ab initio methods. in short and easy form slides. after one time read you can easily understand methods for protein structure prediction.
protein sturcture prediction and molecular modellingDileep Paruchuru
This document discusses molecular modeling and protein structure prediction. It begins by introducing molecular modeling as a combination of computational chemistry and computer graphics that allows scientists to generate and present molecular data. It then discusses the two main computational methods for molecular modeling - molecular mechanics and quantum mechanics. The document goes on to discuss molecular mechanics in more detail and its applications. It also discusses protein structure and function, the challenges of protein structure prediction, and the goals of protein structure prediction.
RNA plays an important role in protein synthesis. It has a primary sequence made of A, C, G, and U nucleotides that can fold into a secondary structure through base pairing. The secondary structure is predicted using either maximizing the number of base pairs or minimizing the free energy. Dynamic programming is commonly used to predict the optimal secondary structure. Predicting RNA structure is important for understanding its function and evolution.
Lit Review Talk by Kato Mivule: A Review of Genetic AlgorithmsKato Mivule
This document summarizes a literature review presentation on genetic algorithms and their application to bioinformatics. It begins with an outline and sources, then provides background on genetics, genetic algorithms, and their process. It reviews a paper applying genetic algorithms to gene expression data classification. The paper achieved higher accuracy than other methods, selecting optimal gene groups to classify cancer types. In conclusion, genetic algorithms can create high quality solutions but may have longer run times than specialized algorithms.
This document discusses protein structure, classification, prediction, and visualization. It covers secondary structure elements like alpha helices and beta sheets, as well as tertiary and quaternary structure. It describes protein structure databases like the Protein Data Bank and tools for visualizing protein structures. Different amino acid properties that influence secondary structure are also discussed.
Presentation 2007 Journal Club Azhar Ali Shahguest5de83e
The document summarizes rapid methods for comparing protein structures and scanning structure databases. It discusses various representations of protein structures used in rapid comparison methods, including strings, arrays, secondary structural elements, and backbone representations. It also reviews different algorithms that use these representations, such as TOPSCAN, PRIDE, SSM, DEJAVU, and VAST. Evaluation of these methods on large databases is needed to properly benchmark their speed and accuracy.
MEME – An Integrated Tool For Advanced Computational ExperimentsGIScRG
The document describes MEME, an integrated tool for advanced computational experiments. MEME allows users to efficiently explore model responses through parameter sweeps and design of experiments. It supports running simulations in parallel on local clusters and grids. MEME collects, analyzes, and visualizes results. It implements intelligent "IntelliSweep" methods like iterative uniform interpolation and genetic algorithms to refine parameter space exploration.
Introduction of Mycobacterium tuberculosis, quinoline and their biological importance. Design, diversity oriented synthesis, primary antimycobacterial activity evaluation against M.smegmatis strain and library generation of bedaquiline related quinolinyl heterocycles. Structure optimization of obtained active hits by using molecular hybridization, ring functionalization and antimycobacterial activity evaluation against M.smegmatis strain. Low cytotoxicity against A549 cells highlighted the efficiency of the hits. Also antimicrobial and anti-inflammatory activities were also carried out. BDMS catalyzed one pot multicomponent synthesis of imidazo[1,2-a]pyridine and Friedlander synthesis of quinolone under solvent free conditions.
A study was carried out to predict the 3D structure and function of an unidentified wheat protein (CAA35597.1) using LOMETS and I-TASSER servers. The servers were able to predict a high quality 3D structure of the wheat protein based on its amino acid sequence. The predicted structure was further analyzed and accepted in the Protein Model Database.
A search engine for phylogenetic tree databases - D. Fernándes-BacaRoderic Page
- PhyloFinder is a search engine for phylogenetic tree databases that allows powerful queries while handling issues like synonymous taxonomic names and misspellings.
- It exploits taxonomic classifications to identify trees containing taxa and their ancestors/descendants. Queries can search for taxa, embedded subtrees, tree similarity, and more.
- PhyloFinder uses techniques like inverted indexes and nested intervals to efficiently store and query trees without loading them into memory. Taxonomic and phylogenetic queries are implemented using boolean operations and LCA comparisons.
Presentation for blast algorithm bio-informaticezahid6
Presentation for BLAST algorithm
Publisher Md.Zahid Hasan
Bio-informatics blast is the use of computational tools for the process of acquisition, visualization, analysis and distribution of these datasets obtained by imaging modalities.
Lead Online Training is an IT training provider that specializes in providing online training courses on technologies like Hadoop, Java, Oracle, and SAP. It offers virtual classroom training as a convenient and effective alternative to on-site training. The company provides training on topics such as custom software development, data warehousing concepts, and Abinitio, covering the architecture, components, ports, files, partitioning, sorting, transforming, working with databases, and more. Lead Online Training aims to teach students and help them pursue careers in IT.
Bioinformatics is the application of information technology to analyze biological data. This document provides an overview of bioinformatics, including publicly available genome sequences from 1998, promises for applications in medicine and biotechnology, the need for bioinformaticians to analyze growing biological databases, common bioinformatics tasks like sequence analysis and molecular modeling, and important databases like GenBank, SwissProt, and NCBI.
This document discusses various methods for aligning and comparing biological sequences like DNA and proteins, including local vs global alignment, exact vs heuristic algorithms, and tools like BLAST, PSI-BLAST, and statistical tests for assessing the significance of sequence similarities. Local alignment finds short similar regions, while global alignment considers the full sequence length. Exact methods are rigorous but slow, while heuristics sacrifice completeness for speed. BLAST uses ungapped segment pairs to identify regions for gapped extension and alignment. PSI-BLAST iteratively reweights sequences based on multiple alignments to identify more distant homologs. Statistical tests compare observed sequence similarities to random expectations to assess biological significance.
Ketone bodies (acetoacetate, beta-hydroxybutyrate, and acetone) are water-soluble molecules produced by the liver from fatty acids during periods of low food intake (fasting or starvation), prolonged intense exercise, and uncontrolled diabetes. The liver exports ketone bodies to be used as an energy source by the brain, heart, and skeletal muscles in place of glucose. Ketone body production is regulated by controlling fatty acid release from adipose tissue, fatty acid oxidation in the liver, and partitioning of acetyl-CoA between ketogenesis and the citric acid cycle. Excessive ketone body accumulation can overwhelm acid-base buffering mechanisms and lead to ketoacidosis, as
Tertiary structure describes how protein chains fold upon themselves into complex 3D shapes. These shapes are stabilized by interactions between amino acid side chains like disulfide bonds, hydrogen bonds, and hydrophobic interactions. Long protein chains often contain multiple domains that fold independently. Quaternary structure refers to complexes of two or more protein subunits. Chaperone proteins assist other proteins in proper folding, while misfolded proteins can accumulate and cause diseases.
This document provides information on various computational tools and methods for protein identification, characterization, and structure prediction. It discusses tools that use amino acid composition, sequence alignment, peptide mass fingerprinting, and physico-chemical properties to identify proteins. It also describes methods such as Chou-Fasman, GOR, and neural networks that predict protein secondary structure and properties based on amino acid order, propensities, and probabilities.
58.Comparative modelling of cellulase from Aspergillus terreusAnnadurai B
The document discusses homology modeling of the cellulase enzyme in Aspergillus terreus. It begins with an abstract that describes cellulase as a widely used hydrolytic enzyme involved in converting biomass to simpler sugars. It then provides details on homology modeling and the steps involved, which include template recognition, alignment, backbone and loop modeling, and model validation. The document discusses modeling of the cellulase protein from Aspergillus terreus using templates from the PDB and visualization software. It evaluates the modeled cellulase structure using validation servers to check accuracy.
The document discusses computational methods for predicting protein structure, specifically homology modeling and threading/fold recognition. Homology modeling constructs a target protein structure using the amino acid sequence and experimental structure of a homologous protein as a template. Threading/fold recognition predicts a protein's structural fold by fitting its sequence to structures in a database and selecting the best fitting fold, either through an energy-based method or profile-based method. Both methods are limited as homology modeling relies on a template structure and threading/fold recognition may not find a match if the correct fold does not exist in the database.
HERE IN THIS PRESENTATION HY HOMOLOGY MODELING IS EXPLAIN , WITH EXAMPLES OF PROTEIN PRIMARY AND SECONDARY, SHOWING THE IMAGES FORM WHICH MAKES EASY TO UNDERSTAND
The document discusses protein structure modeling through homology modeling. It describes the key steps in homology modeling which include: (1) finding a suitable template through database searches, (2) aligning the target sequence to the template, (3) assigning coordinates from conserved regions of the template, (4) building loops and variable regions either from other structures or de novo, (5) searching for optimal side chain conformations, and (6) refining the model through molecular mechanics. The document emphasizes validating the final model to identify any inherent errors from the template or modeling process.
Computational Prediction Of Protein-1.pptxashharnomani
This document discusses computational methods for predicting protein structure, including homology modeling, fold recognition/threading, and ab initio prediction. Homology modeling predicts structure based on sequence similarity to proteins with known structures. It involves aligning the target sequence to template structures, then modeling secondary structure, loops, and side chains. Accuracy depends on template quality and sequence identity above 30%. Fold recognition matches sequences to structure folds without clear homology. Ab initio prediction predicts structure from sequence alone using physics-based forces.
This document discusses different methods for predicting the secondary structure of proteins, including statistical methods like Chou-Fasman and GOR that use amino acid frequencies, and neural network methods like PHD that use multiple sequence alignments and training sets of known structures. It also briefly outlines experimental methods for determining protein structure like X-ray crystallography, NMR spectroscopy, and cryo-electron microscopy.
Homology modeling uses the amino acid sequence of a target protein and the 3D structure of a related template protein to generate a 3D model of the target. It involves aligning the target sequence to the template sequence, building the backbone of the target based on the template structure, modeling loops and side chains, optimizing the model structure, and validating the model. Homology modeling is most accurate when the sequence identity between the target and template is above 30%. It provides information about conserved regions and residues but is limited in modeling insertions, deletions, and side chains.
Homology modeling uses the amino acid sequence of a target protein and the 3D structure of an evolutionarily related template protein to generate a model of the target protein's structure. It involves searching for a template, aligning the target and template sequences, building the target protein backbone based on the template structure, modeling loops and side chains, optimizing the model structure, and validating the model. Homology modeling is most accurate when the sequence identity between the target and template is above 30%. It provides useful information about conserved regions and residues but has limitations for modeling insertions, deletions, and side chains.
Comparative Protein Structure Modeling and itsApplicationsLynellBull52
Comparative Protein Structure Modeling and its
Applications to Drug Discovery
Matthew Jacobson
1
and Andrej Sali
1,2
1
Department of Pharmaceutical Chemistry, California Institute for
Quantitative Biomedical Research, Mission Bay Genentech Hall, 600 16th Street,
University of California, San Francisco, CA 94143-2240, USA
2
Department of Biopharmaceutial Sciences, California Institute for
Quantitative Biomedical Research, Mission Bay Genentech Hall, 600 16th Street,
University of California, San Francisco, CA 94143-2240, USA
Contents
1. Introduction 259
2. Fold assignment and sequence-structure alignment 261
3. Comparative model building 261
4. Loop modeling 262
5. Sidechain modeling 263
6. Comparative modeling by MODELLER 264
7. Physics-based approaches to comparative model construction and refinement 264
8. Accuracy of comparative models 266
9. Modeling on a genomic scale 266
10. Applications of comparative modeling to drug discovery 267
10.1. Comparative models vs experimental structures in virtual screening 267
10.2. Use of comparative models to obtain novel drug leads 268
10.3. Comparative models of kinases in virtual screening 269
10.4. GPCR comparative models for drug development 270
10.5. Other uses of comparative models in drug development 271
10.6. Future directions 272
11. Conclusions 273
References 273
1. INTRODUCTION
Homology or comparative protein structure modeling constructs a three-dimensional
model of a given protein sequence based on its similarity to one or more known
structures. In this perspective, we begin by describing the comparative modeling
technique and the accuracy of the models. We then discuss the significant role that
comparative prediction plays in drug discovery. We focus on virtual ligand screening
against comparative models and illustrate the state-of-the-art by a number of specific
examples.
The genome sequencing efforts are providing us with complete genetic blueprints for
hundreds of organisms, including humans. We are now faced with describing,
ANNUAL REPORTS IN MEDICINAL CHEMISTRY, VOLUME 39 q 2004 Elsevier Inc.
ISSN: 0065-7743 DOI 10.1016/S0065-7743(04)39020-2 All rights reserved
controlling, and modifying the functions of proteins encoded by these genomes. This
task is generally facilitated by protein three-dimensional structures [1], which are best
determined by experimental methods such as X-ray crystallography and nuclear
magnetic resonance (NMR) spectroscopy. Despite significant advances in these
techniques, many protein sequences are not easily accessible to structure determination
by experiment. Over the last two years, the number of sequences in the comprehensive
public sequence databases, such as SwissProt/TrEMBL [2] and GenPept [3], increased
by a factor of 2.3 from 522,959 to 1,215,803 on 26 April 2004. In contrast, despite
structural genomics, the number of experimentally determined structures deposited in
the Protein Data Bank (PDB) increas ...
Structural genomics is a field that aims to determine the 3D structures of all proteins encoded by a genome. It involves determining structures on a large scale using techniques like X-ray crystallography and NMR. This allows identification of novel protein folds and potential drug targets. Comparative genomics compares genomic features between organisms and provides insights into evolution and conserved sequences and functions. It is a key tool in fields like medicine and agriculture.
Protein struc pred-Ab initio and other methods as a short introduction.ppt60BT119YAZHINIK
This document discusses different levels of protein structure from primary to quaternary structure. It then summarizes various methods for protein structure prediction including comparative modeling, fold recognition, fragment assembly, and ab initio methods. Comparative modeling is the most common approach, using structural templates that are similar in sequence to the target protein. Fold recognition and fragment assembly methods can also predict structure without strong sequence similarity. Ab initio methods aim to predict structure directly from physical principles rather than existing structural data.
This document discusses protein secondary structure and methods for predicting it. It introduces protein secondary structure including alpha helices and beta pleated sheets. It then describes several common methods for predicting secondary structure from a protein's amino acid sequence, such as the Chou-Fasman method, nearest neighbor method, hidden Markov models, neural networks, and multiple sequence alignments. The accurate prediction of protein secondary structure from sequence is important for understanding protein structure and function.
This document discusses homology modeling, which is a computational technique used to develop atomic-resolution models of proteins based on their amino acid sequences and known 3D structures of homologous proteins. It describes the key steps in homology modeling as template identification, target-template alignment, model building and refinement, and model validation. The advantages of homology modeling include that it is faster than experimental techniques. However, the accuracy depends on factors like the sequence identity between the target and template.
This document discusses various methods for predicting protein function from sequence and structure. It begins by explaining the importance of predicting protein function for applications like disease diagnosis and drug discovery. It then outlines different types of data that can be used for functional prediction, including sequence, structure, expression profiles, and interactions. Both sequence-based methods like homology searches and domain identification as well as structure-based approaches are covered. Specific tools discussed include BLAST, Pfam, SCOP, CATH, and ProFunc. The document emphasizes that functional prediction is challenging given proteins can have multiple functions and homology does not always imply similar function. It also notes limitations of simple homology searches.
HMM’S INTERPOLATION OF PROTIENS FOR PROFILE ANALYSISijcseit
HMM has found its application in almost every field. Applying Hmm to biological sequences has its own
advantages. HMM’s being more systematic and specific, yield a result better than consensus techniques.
Profile HMMs use position specific scoring for the matching & substitution of a residue and for the
opening or extension of a gap. HMMs apply a statistical method to estimate the true frequency of a residue
at a given position in the alignment from its observed frequency while standard profiles use the observed
frequency itself to assign the score for that residue. This means that a profile HMM derived from only 10 to
20 aligned sequences can be of equivalent quality to a standard profile created from 40 to 50 aligned
sequences.
Performance Improvement of BLAST with Use of MSA Techniques to Search Ancesto...journal ijrtem
process in which instead comparing whole query sequence with database sequence it breaks
query sequence into small words and these words are used to align patterns. it uses heuristic method which
make it faster than earlier smith-waterman algorithm. But due small query sequence used for align in case of
very large database with complex queries it may perform poor. To remove this draw back we suggest by using
MSA tools which can filter database in by removing unnecessary sequences from data. This sorted data set then
applies to BLAST which can then indentify relationship among them i.e. HOMOLOGS, ORTHOLOGS,
PARALOGS. The proposed system can be further use to find relation among two persons or used to create
family tree. Ortholog is interesting for a wide range of bioinformatics analyses, including functional annotation,
phylogenetic inference, or genome evolution. This system describes and motivates the algorithm for predicting
orthologous relationships among complete genomes. The algorithm takes a pairwise approach, thus neither
requiring tree reconstruction nor reconciliation
Performance Improvement of BLAST with Use of MSA Techniques to Search Ancesto...IJRTEMJOURNAL
BLAST is most popular sequence alignment tool used to align bioinformatics patterns. It uses
local alignment process in which instead comparing whole query sequence with database sequence it breaks
query sequence into small words and these words are used to align patterns. it uses heuristic method which
make it faster than earlier smith-waterman algorithm. But due small query sequence used for align in case of
very large database with complex queries it may perform poor. To remove this draw back we suggest by using
MSA tools which can filter database in by removing unnecessary sequences from data. This sorted data set then
applies to BLAST which can then indentify relationship among them i.e. HOMOLOGS, ORTHOLOGS,
PARALOGS. The proposed system can be further use to find relation among two persons or used to create
family tree. Ortholog is interesting for a wide range of bioinformatics analyses, including functional annotation,
phylogenetic inference, or genome evolution. This system describes and motivates the algorithm for predicting
orthologous relationships among complete genomes. The algorithm takes a pairwise approach, thus neither
requiring tree reconstruction nor reconciliation
Psychrophilic (cold-adapted) microorganisms make a major contribution
to Earth’s biomass and perform critical roles in global biogeochemical cycles.
The vast extent and environmental diversity of Earth’s cold biosphere
has selected for equally diverse microbial assemblages that can include archaea,
bacteria, eucarya, and viruses. Underpinning the important ecological
roles of psychrophiles are exquisite mechanisms of physiological adaptation.
Psychrophilic (cold-adapted) microorganisms make a major contribution
to Earth’s biomass and perform critical roles in global biogeochemical cycles.
The vast extent and environmental diversity of Earth’s cold biosphere
has selected for equally diverse microbial assemblages that can include archaea,
bacteria, eucarya, and viruses. Underpinning the important ecological
roles of psychrophiles are exquisite mechanisms of physiological adaptation.
Evolution has also selected for cold-active traits at the level of molecular
adaptation, and enzymes from psychrophiles are characterized by specific
structural, functional, and stability properties. These characteristics of enzymes
from psychrophiles not only manifest in efficient low-temperature
activity, but also result in a flexible protein structure that enables biocatalysis
in nonaqueous solvents. In this review, we examine the ecology of Antarctic
psychrophiles, physiological adaptation of psychrophiles, and properties of
cold-adapted proteins, and we provide a view of how these characteristics
inform studies of astrobiology.
Marine microbiology ecology & applications colin munnRainu Rajeev
This document provides metadata and contents for the book "Marine Microbiology: Ecology and Applications" by C.B. Munn. It includes information on the title, author, publisher, and publication date. The contents section lists 15 chapters that will cover topics such as methods in marine microbiology, structure and physiology of marine prokaryotes, and diversity of marine bacteria and archaea.
All living organisms have the ability
to improve themselves through
natural means in order to adapt to
changing environmental conditions.
However, it takes hundreds of years
before any detectable improvement
is obtained. Man then learned how
to domesticate and breed plants
in order to develop crops to his
own liking and needs using various
means including biotechnology.
Biotechnology is defined as
a set of tools that uses living
organisms (or parts of organisms)
to make or modify a product,
improve plants, trees or animals,
or develop microorganisms
for specific uses. Agricultural
biotechnology is the term used in
crop and livestock improvement
through biotechnology tools. This
monograph will focus only on
agricultural crop biotechnology.
Biotechnology encompasses a
number of tools and elements of
conventional breeding techniques,
bioinformatics, microbiology,
molecular genetics, biochemistry,
plant physiology, and molecular
biology.
The biotechnology tools that
are important for agricultural
biotechnology include:
- Conventional plant breeding
- Tissue culture and
micropropagation
- Molecular breeding or marker
assisted selection
- Genetic engineering and GM
crops
- Molecular Diagnostic Tools
The Marine Board provides a pan-European platform
for its member organisations to develop common priorities,
to advance marine research, and to bridge the
gap between science and policy in order to meet future
marine science challenges and opportunities.
The Marine Board was established in 1995 to facilitate
enhanced cooperation between European marine science
organisations (both research institutes and research
funding agencies) towards the development of a common
vision on the research priorities and strategies for
marine science in Europe. In 2012, the Marine Board
represents 34 Member Organisations from 20 countries.
The marine Board provides the essential components for
transferring knowledge for leadership in marine research
in Europe. Adopting a strategic role, the Marine Board
serves its member organisations by providing a forum
within which marine research policy advice to national
agencies and to the European Commission is developed,
with the objective of promoting the establishment of the
European Marine Research Area.
This document provides an overview of the field of bioinformatics. It discusses that bioinformatics is the analysis of biological information using computers and statistical techniques, and involves organizing, storing, analyzing and visualizing genomic data. It also discusses various databases used in bioinformatics, including nucleotide sequence databases like GenBank, protein sequence databases like Swiss-Prot, structure databases like PDB, and species-oriented databases. Examples of analyzing genomic sequences, predicting protein structures, and correlating gene expression and disease are also provided.
Or: Beyond linear.
Abstract: Equivariant neural networks are neural networks that incorporate symmetries. The nonlinear activation functions in these networks result in interesting nonlinear equivariant maps between simple representations, and motivate the key player of this talk: piecewise linear representation theory.
Disclaimer: No one is perfect, so please mind that there might be mistakes and typos.
dtubbenhauer@gmail.com
Corrected slides: dtubbenhauer.com/talks.html
Travis Hills' Endeavors in Minnesota: Fostering Environmental and Economic Pr...Travis Hills MN
Travis Hills of Minnesota developed a method to convert waste into high-value dry fertilizer, significantly enriching soil quality. By providing farmers with a valuable resource derived from waste, Travis Hills helps enhance farm profitability while promoting environmental stewardship. Travis Hills' sustainable practices lead to cost savings and increased revenue for farmers by improving resource efficiency and reducing waste.
Authoring a personal GPT for your research and practice: How we created the Q...Leonel Morgado
Thematic analysis in qualitative research is a time-consuming and systematic task, typically done using teams. Team members must ground their activities on common understandings of the major concepts underlying the thematic analysis, and define criteria for its development. However, conceptual misunderstandings, equivocations, and lack of adherence to criteria are challenges to the quality and speed of this process. Given the distributed and uncertain nature of this process, we wondered if the tasks in thematic analysis could be supported by readily available artificial intelligence chatbots. Our early efforts point to potential benefits: not just saving time in the coding process but better adherence to criteria and grounding, by increasing triangulation between humans and artificial intelligence. This tutorial will provide a description and demonstration of the process we followed, as two academic researchers, to develop a custom ChatGPT to assist with qualitative coding in the thematic data analysis process of immersive learning accounts in a survey of the academic literature: QUAL-E Immersive Learning Thematic Analysis Helper. In the hands-on time, participants will try out QUAL-E and develop their ideas for their own qualitative coding ChatGPT. Participants that have the paid ChatGPT Plus subscription can create a draft of their assistants. The organizers will provide course materials and slide deck that participants will be able to utilize to continue development of their custom GPT. The paid subscription to ChatGPT Plus is not required to participate in this workshop, just for trying out personal GPTs during it.
Describing and Interpreting an Immersive Learning Case with the Immersion Cub...Leonel Morgado
Current descriptions of immersive learning cases are often difficult or impossible to compare. This is due to a myriad of different options on what details to include, which aspects are relevant, and on the descriptive approaches employed. Also, these aspects often combine very specific details with more general guidelines or indicate intents and rationales without clarifying their implementation. In this paper we provide a method to describe immersive learning cases that is structured to enable comparisons, yet flexible enough to allow researchers and practitioners to decide which aspects to include. This method leverages a taxonomy that classifies educational aspects at three levels (uses, practices, and strategies) and then utilizes two frameworks, the Immersive Learning Brain and the Immersion Cube, to enable a structured description and interpretation of immersive learning cases. The method is then demonstrated on a published immersive learning case on training for wind turbine maintenance using virtual reality. Applying the method results in a structured artifact, the Immersive Learning Case Sheet, that tags the case with its proximal uses, practices, and strategies, and refines the free text case description to ensure that matching details are included. This contribution is thus a case description method in support of future comparative research of immersive learning cases. We then discuss how the resulting description and interpretation can be leveraged to change immersion learning cases, by enriching them (considering low-effort changes or additions) or innovating (exploring more challenging avenues of transformation). The method holds significant promise to support better-grounded research in immersive learning.
EWOCS-I: The catalog of X-ray sources in Westerlund 1 from the Extended Weste...Sérgio Sacani
Context. With a mass exceeding several 104 M⊙ and a rich and dense population of massive stars, supermassive young star clusters
represent the most massive star-forming environment that is dominated by the feedback from massive stars and gravitational interactions
among stars.
Aims. In this paper we present the Extended Westerlund 1 and 2 Open Clusters Survey (EWOCS) project, which aims to investigate
the influence of the starburst environment on the formation of stars and planets, and on the evolution of both low and high mass stars.
The primary targets of this project are Westerlund 1 and 2, the closest supermassive star clusters to the Sun.
Methods. The project is based primarily on recent observations conducted with the Chandra and JWST observatories. Specifically,
the Chandra survey of Westerlund 1 consists of 36 new ACIS-I observations, nearly co-pointed, for a total exposure time of 1 Msec.
Additionally, we included 8 archival Chandra/ACIS-S observations. This paper presents the resulting catalog of X-ray sources within
and around Westerlund 1. Sources were detected by combining various existing methods, and photon extraction and source validation
were carried out using the ACIS-Extract software.
Results. The EWOCS X-ray catalog comprises 5963 validated sources out of the 9420 initially provided to ACIS-Extract, reaching a
photon flux threshold of approximately 2 × 10−8 photons cm−2
s
−1
. The X-ray sources exhibit a highly concentrated spatial distribution,
with 1075 sources located within the central 1 arcmin. We have successfully detected X-ray emissions from 126 out of the 166 known
massive stars of the cluster, and we have collected over 71 000 photons from the magnetar CXO J164710.20-455217.
Remote Sensing and Computational, Evolutionary, Supercomputing, and Intellige...University of Maribor
Slides from talk:
Aleš Zamuda: Remote Sensing and Computational, Evolutionary, Supercomputing, and Intelligent Systems.
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Inter-Society Networking Panel GRSS/MTT-S/CIS Panel Session: Promoting Connection and Cooperation
https://www.etran.rs/2024/en/home-english/
When I was asked to give a companion lecture in support of ‘The Philosophy of Science’ (https://shorturl.at/4pUXz) I decided not to walk through the detail of the many methodologies in order of use. Instead, I chose to employ a long standing, and ongoing, scientific development as an exemplar. And so, I chose the ever evolving story of Thermodynamics as a scientific investigation at its best.
Conducted over a period of >200 years, Thermodynamics R&D, and application, benefitted from the highest levels of professionalism, collaboration, and technical thoroughness. New layers of application, methodology, and practice were made possible by the progressive advance of technology. In turn, this has seen measurement and modelling accuracy continually improved at a micro and macro level.
Perhaps most importantly, Thermodynamics rapidly became a primary tool in the advance of applied science/engineering/technology, spanning micro-tech, to aerospace and cosmology. I can think of no better a story to illustrate the breadth of scientific methodologies and applications at their best.
2. Protein Structural Bioinformatics
Definition
The subdiscipline of bioinformatics that focuses on the
representation, storage, retrieval, analysis, and display of
structural information at the atomic and subcellular spatial
scales.
(From Structural Bioinformatics, by P.E. Bourne & H. Weissig (eds.), John Wiley &
Sons, Inc., 2003, pp.4.)
Why is STRUCTURAL bioinformatics important?
Because a protein’s function is determined by its structure.
Knowledge of a protein’s structure is necessary in order to gain
a full understanding of the biological role of a protein.
3. Bioinformatics methods can be used to analyze
protein structural data in the following ways:
• Visualization of protein structures
• Alignment of protein structures
• Classification of proteins into families, based on similarity
of their structures
• Prediction of protein structures
• Simulation of protein folding and dynamic motions
4. Protein structure determination by x-ray crystallography or
NMR is difficult (see Powerpoint slides from last module).
It takes 1-3 years to solve a protein structure by these methods. Certain
proteins, such as membrane proteins, are extremely difficult or impossible to
solve by these methods. Due to genomic sequencing efforts, the gap
between known protein sequences and known protein structures is
increasing– only about 3,000 unique protein structures have been
determined, but over 1 million unique sequences have been determined.
Therefore, it is necessary to use bioinformatics methods to predict the
structures of proteins for which a crystal structure or NMR structure has not
been determined.
Bioinformatics methods can predict:
(1) secondary structural elements in a protein sequence
(2) the tertiary structure of the entire sequence
(3) “special” structures, such as transmembrane a-helices,
transmembrane b-barrels, coiled coils, and leucine zippers
5. Protein Secondary Structure Prediction
All secondary structure prediction is based on the assumption that there
should be a correlation between amino acid sequence and secondary
structure– in other words, it is assumed that certain stretches of amino acids
are more likely to form one type of secondary structure than another.
During secondary structure prediction, the conformational state of each
residue in a protein sequence is predicted; generally each residue is
predicted as having one of three possible states:
(1) a-helical structure
(2) b-strand
(3) “other” (b-turn, loop, or random coil)
Sometimes b-turn is separated as a 4th state.
Why is prediction of secondary structure useful?
It can help guide sequence alignment or improve existing sequence
alignment of distantly related sequences. It is also an intermediate step in
some methods for tertiary structure prediction.
6. Methods of secondary structure prediction fall into
two broad classes:
Ab initio methods– predict secondary structure based solely
on protein sequence; these methods compute statistics for the
residues that occur in different secondary structural elements in
proteins with known structures, in order to identify “patterns” in
the types of residues that occur in a given type of secondary
structure.
Homology-based methods– make use of multiple sequence
alignments of homologous proteins to predict secondary
structure; these methods are able to locate conserved patterns
that are characteristic of particular secondary structural
elements across the aligned family members.
7. Certain amino acids are observed more frequently than others in a-
helices, b-strands, and b-turns in crystal structures (see Figure). This
leads to the idea that each amino acid tends to “prefer” being
constrained in a certain type of secondary structure, or has an
“intrinsic propensity” to adopt that secondary structure.
Fig. 4-10 from Lehninger Principles of Biochemistry, 4th ed.
The figure shows that:
Glu, Met, Ala are most
frequent in a-helices
Val, Tyr, Ile are most
frequent in b-strands
Pro, Gly, Asn are most
frequent in b-turns
Based on this data, it
is believed that Glu
has a high a-helical
propensity, but a low
b-strand propensity.
8. Ab initio methods of secondary structure prediction:
• These methods calculate the relative propensity (intrinsic tendency) of each
amino acid in a protein sequence to belong to a certain secondary structural
element.
• Propensity scores for the 20 amino acids are derived from known protein
structures: these propensities are calculated from the relative frequency of a
given amino acid within the proteins, its frequency in a given type of
secondary structure, and the fraction of all amino acids occurring in that type
of secondary structure.
• Stretches of a protein’s sequence that contain many residues with a high a-
helical propensity are predicted to fold into a-helices. Stretches of sequence
that contain many residues with a high b-strand propensity are predicted to
fold into b-strands.
• Two examples: Chou-Fasman method, GOR method
9. Accuracy of ab initio methods:
• These methods are not very accurate:
• Chou-Fasman method, 50%-60% accuracy
• GOR method, 64% accuracy, drastically underpredicts b-strands
• These methods are only a little better than randomly assigning secondary
structure! Known proteins consist of ~31% a-helix and ~28% b-sheet, so
randomly assigning secondary structural elements to residues would result in
~30% accuracy.
• Specific problems with these methods:
• Tend to underpredict the lengths of a-helices and b-strands– can’t
identify the first and last residues of helices and strands very well
• Tend to miss b-strands completely
10. A few homology-based 2o structure prediction methods:
Neural network methods:
PROFsec (an improved version of PHDsec)
http://www.predictprotein.org/
PSIPRED
http://bioinf.cs.ucl.ac.uk/psipred/
SSpro (newest version is 4.0)
http://scratch.proteomics.ics.uci.edu/
SAM-T (SAM-T08 is newest version; SAM-T06, SAM-T02, SAM-T99-- old versions)
http://compbio.soe.ucsc.edu/SAM_T08/T08-query.html
Nearest-neighbor methods:
NNSSP
no longer available online
PREDATOR
http://mobyle.pasteur.fr/cgi-bin/portal.py?#forms::predator
HMM methods:
HMMSTER
http://www.bioinfo.rpi.edu/~bystrc/hmmstr/server.php
11. A few methods for predicting transmembrane a-helices:
TMHMM
http://www.cbs.dtu.dk/services/TMHMM/
HMMTOP
http://www.enzim.hu/hmmtop/index.html
Phobius (also predicts presence of signal peptides)
http://phobius.sbc.su.se/
TopPred
http://mobyle.pasteur.fr/cgi-bin/portal.py?#forms::toppred
PRED-TMR
http://athina.biol.uoa.gr/PRED-TMR/
DAS
http://mendel.imp.ac.at/sat/DAS/DAS.html
TMpred
http://www.ch.embnet.org/software/TMPRED_form.html
MEMSAT
http://bioinf.cs.ucl.ac.uk/psipred/
Accuracies of the methods:
Levels of accuracy are reported by the developers to be in the range of 75-95%.
At least one study (2001) found TMHMM to be the best performing program.
It is best to use several methods and compare the results to arrive at a consensus
prediction. When different methods, specifically methods that are based on different
algorithms, give similar results, the reliability of the results is higher.
12. Tertiary structure prediction methods fall into three
classes:
(1) Homology modeling (also called comparative modeling)
A structure is built based on the known structure of another protein that is
similar in sequence (a homolog).
(2) Threading (also called structural fold recognition)
A structure is predicted for a protein by “threading” its sequence through a
variety of known structures to determine which structure the sequence best
fits.
(3) Ab initio prediction (also called de novo prediction)
A structure is predicted based only on the amino acid sequence of the
protein, using the physicochemical properties of its residues and the
principles governing protein folding.
13. Homology modeling for tertiary structure prediction:
Homology modeling is based on the idea that if two proteins share a high
degree of sequence similarity (i.e., they are close homologs), they are likely
to have very similar 3D structures. In general, proteins that share >30%
sequence identity are likely to be quite similar in structure.
Therefore, if a protein of unknown structure is similar in sequence to a
protein of known structure, the known structure can be used as a template to
which the unknown sequence is fit. The structure that is built for the
unknown sequence is then called a homology model for the structure of that
sequence.
The “safe homology
modeling zone,” above the
gray curve, is the region
where two proteins are likely
to have the same structure.
Fig. 5 from R. Nair & B. Rost,
Protein Science (2002) 11: 2836-47.
14. Steps in homology modeling for tertiary structure
prediction:
The protein of unknown structure for which a structural model is to be built
will be called the “target sequence.”
1. Template selection– Identify protein(s) in the PDB that are
homologous to the target sequence using BLAST or PSI-BLAST. If a close
homolog with known structure is found, its structure will serve as a template
to which the target sequence will be matched. The template should have
at least 30% sequence identity with the target. (Proteins that share less
than 30% sequence identity may not be similar enough in structure to carry
out homology modeling.) If PSI-BLAST does not identify a suitable template,
it will probably be necessary to construct a structural model by threading.
It is possible to use multiple templates if more than one good template is
identified. When multiple templates are available, it is best to use more than
one template to avoid biasing the model toward a single protein. The
template used in the next step of homology modeling will then be an
averaged structure based on all of the chosen templates.
15. Steps in homology modeling for tertiary structure
prediction:
2. Sequence alignment– Construct a multiple sequence alignment of
the target, the template, and other homologous sequences. It is actually the
alignment of the target and template that is of interest, but the inclusion of
other homologs provides more information, helping to ensure that the best
alignment of homologous residues is achieved. The quality of the target-
template alignment is critical for constructing an accurate structural
model for the target. If a given residue in the target is not aligned with the
proper residue in the template, the error cannot be corrected in later steps of
model building. A robust multiple sequence alignment program should be
used for this step, and the resulting alignment should be very carefully
examined and manually refined if necessary.
16. Steps in homology modeling for tertiary structure
prediction:
3. Backbone model building– Residues in the aligned regions of the
target and template are assumed to adopt the same structure. Therefore,
the backbone atoms of these residues in the target can be placed in the
same 3D location as the backbone atoms of these residues in the template.
See the alignment below as an example.
Target: ...FKSQAAIHEAYCNFHYKVTAAASRTPEIDFDVHFSSIF...
Template: ...FKQQANIHCAYCNGAYKIG-------GKELQVHFSWLF...
For these residues, backbone atoms of the target are assumed
to occupy the same 3D location as those of the template.
F aligned with F. They are identical,
so all atoms of target F will overlap
the 3D positions of all atoms of
template F.
E aligned with D. They are not identical, but
their backbone atoms can be assumed to
occupy the same 3D position. So backbone
atoms of target D will overlap the 3D
positions of backbone atoms of template E.
17. Steps in homology modeling for tertiary structure prediction:
4. Loop building– There are likely to be regions in the alignment where
gaps appear because the target sequence does not match the template. The
target sequence residues in these gap regions are assumed to form a loop that
is not present in the template structure. The structure of this loop can be built
using several different methods. In any case, it is a difficult problem since the
template provides no information to guide the building of the loop structure.
Target: ...FKSQAAIHEAYCNFHYKVTAAASRTPEIDFDVHFSSIF...
Template: ...FKQQANIHCAYCNGAYKIG-------GKELQVHFSWLF...
“Extra” residues in the target sequence do not
match the template and are assumed to form a loop.
target loop
18. Steps in homology modeling for tertiary structure
prediction:
5. Side chain addition– The side chains are added to the backbone
structure. Each side chain could potentially have many possible
conformations due to bond rotation, but steric clashes with neighboring
atoms are not allowed. Therefore, side chain that have the lowest interaction
energy with nearby atoms are chosen.
Target: ...FKSQAAIHEAYCNFHYKVTAAASRTPEIDFDVHFSSIF...
Template: ...FKQQANIHCAYCNGAYKIG-------GKELQVHFSWLF...
Target and template are both F, so
all atoms of the target side chain
can be modeled as having the same
3D positions as the template side
chain, at least initially. (Small
changes in position may be
necessary in later refinement steps.)
Target and template have different
side chains (D vs. E), so the side
chain rotamer that is chosen for the
target D must not overlap/clash with
any neighboring atoms.
19. Steps in homology modeling for tertiary structure
prediction:
6. Model refinement– Unfavorable bond angles, bond lengths, and
atom contacts are likely to exist in the preliminary model, so an energy
minimization procedure is applied to refine the model. In this procedure,
atom positions are shifted so that the overall conformation of the entire
structure has the lowest energy potential. Only limited energy minimization
should be applied (a few hundred iterations) so that major errors are
removed but residues are not moved from their correct positions.
7. Model evaluation– The model is checked for anomalies in dihedral
angles, bond lengths, and atom contacts.
20. Programs for homology modeling:
Many programs for automated homology modeling are now available, so
anyone can construct a homology model on a regular PC. However,
construction of a “good” homology model (at least for sequences that are not
highly similar) usually requires some expertise and usually should be done
with human intervention, rather than in a fully automated fashion.
A few of the freely available programs for homology
modeling:
SWISS-MODEL– Produces accurate models; fast; good tutorials available.
http://swissmodel.expasy.org/
I-TASSER– Produces accurate models; easy to use, but slow
http://zhanglab.ccmb.med.umich.edu/I-TASSER/
Modeller– must be downloaded and installed locally
http://salilab.org/modeller/modeller.html
WHAT IF
http://swift.cmbi.ru.nl/servers/html/index.html
http://swift.cmbi.ru.nl/whatif/
21. Is a homology model CORRECT?
Since the actual (experimentally determined) structure of the target is not
known, there is no way to say whether or not the homology model is
“correct.” Instead, the best a researcher can do is compare the homology
model to the structure of the template from which it was derived. If the atom
positions in the model do not deviate very much from those of the template,
the homology model is said to be “accurate.” The greater the deviation
between model and template, the lower the accuracy of the model.
When is a homology model definitely INCORRECT?
A homology model has regions that are incorrect if it contains structural
features that do not occur in native proteins, such as:
• Hydrophobic side chains on the surface of the model (these side
chains should be buried)
• Unreasonable bond lengths or angles
• Unfavorable noncovalent contacts between atoms (clashes)
• Unreasonable dihedral angles
22. Accuracy of homology modeling:
The template selection and alignment accuracy are crucial to the accuracy of a homology
model. The accuracy of the model depends on the percentage of sequence identity
between the target and template. The average coordinate agreement between the
modeled structure and the actual structure drops ~0.3 Å for each 10% reduction in
sequence identity.
The largest structural differences between homologous proteins are in surface loops. In
other words, the structure of the protein core is more highly conserved. Therefore, the
regions that are most likely to be in error in a homology model are the surface loops.
High-accuracy homology models can be built when the target and template have 50%
or greater sequence identity. Errors are mostly mistakes in side-chain packing, small
shifts of the core backbone regions, and occasionally larger errors in loops.
Medium-accuracy homology models can be built when the proteins share 30-50%
sequence identity. There can be alignment mistakes, and there are more frequent side-
chain packing, core distortion, and loop modeling errors.
Low-accuracy homology models are based on proteins that share <30% sequence
identity. If a model is based on an almost insignificant alignment to a known structure, the
model may have an entirely incorrect fold.
The best model-building programs will produce models of similar accuracy, provided that
the methods are used optimally.