This document discusses de novo protein structure prediction, which predicts protein structure from amino acid sequence alone without using existing protein templates. It notes the need for ab initio prediction when no homologous structures exist. Successful de novo prediction requires an accurate energy function to identify native structures, an efficient conformational search method, and ability to select native models. Results from ab initio prediction typically have 5-10 Angstrom accuracy. Domain prediction is important to divide large proteins into independently folding domains for prediction. Advantages include automation and ability to structurally annotate genomes. Challenges include the vast conformational search space and need for accurate energy functions.
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.
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.
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.
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
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:
Homology modeling is a technique used to predict the 3D structure of a protein from its amino acid sequence by comparing it to proteins with similar sequences whose structures are already known. It involves searching a database for template structures, aligning the target sequence to the template, building a model by transferring 3D coordinates from the template to the target sequence, and validating the resulting model. Homology modeling works best when the sequence identity between the target and template is over 30% since protein structure is more conserved than sequence over evolution.
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.
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.
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.
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.
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
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:
Homology modeling is a technique used to predict the 3D structure of a protein from its amino acid sequence by comparing it to proteins with similar sequences whose structures are already known. It involves searching a database for template structures, aligning the target sequence to the template, building a model by transferring 3D coordinates from the template to the target sequence, and validating the resulting model. Homology modeling works best when the sequence identity between the target and template is over 30% since protein structure is more conserved than sequence over evolution.
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.
Homology modeling, also known as comparative modeling of protein, refers to constructing an atomic-resolution model of the "target" protein from its amino acid sequence and an experimental three-dimensional structure of a related homologous protein.
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.
This document discusses motifs, which are nucleotide or amino acid sequence patterns associated with biological functions. It defines motifs, patterns, and profiles. Motifs are conserved regions, patterns are qualitative expressions, and profiles are quantitative representations. It discusses tools for de novo prediction of motifs like MEME and resources for motif discovery. Finally, it provides examples of motifs, patterns, and building position specific scoring matrices from sample sequences.
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
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.
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.
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
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
Bioinformatic tools can be applied throughout the drug design process to reduce costs and time. High-throughput screening allows testing of millions of compounds against protein targets. Computer modeling predicts compound activity and allows virtual screening. Molecular modeling visualizes compound-protein interactions to understand mechanisms of action. In silico models predict absorption, distribution, metabolism, and excretion to evaluate drug properties without animal testing. Bioinformatics databases provide protein and compound structure information to inform drug target and lead identification. Together these tools automate and accelerate key steps in drug design and development.
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 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.
ESTs are short sequences of DNA that represent genes expressed in certain tissues or organisms. They provide a quick and inexpensive way for scientists to discover new genes and map their positions in genomes. ESTs represent a snapshot of genes expressed in a tissue at a given time. Sequencing the beginning or end of cDNA clones produces 5' and 3' ESTs, which can help identify genes and study gene expression and regulation.
Proteins : is made of chain of amino acids ( amino acid= monomers) therefor the protein is polymers .
The proteins are made up of carbon, hydrogen, oxygen, and nitrogen.
Amino acid :
The document discusses Ramachandran plots, which are used to visualize allowed regions of dihedral angles phi and psi in protein backbone structures. Ramachandran plots show amino acid residues as dots in a two-dimensional map based on their phi and psi angles. Most residues cluster in favored regions corresponding to alpha helices and beta sheets. The document outlines how Ramachandran plots are constructed and analyzed using various software, and their applications in validating protein structures and understanding relationships between structure and amino acid sequence.
This document discusses motifs and domains in proteins. It defines motifs as short conserved regions related to function, such as binding sites, that are not detectable by sequence searches. There are sequence motifs consisting of nucleotide or amino acid patterns, and structural motifs formed by amino acid spatial arrangements. Domains are stable, independently folding units of proteins that determine structure and function. Both motifs and domains are useful for classifying protein families and have structural and functional roles, though domains are more stable independently. Motifs and domains form through interactions of alpha helices and beta sheets and have similarities, but domains mainly determine unique functions while motifs mainly provide structural roles within families.
Clustal Omega is a fast and scalable program for multiple sequence alignment. It begins by producing pairwise alignments using a word-based heuristic method. It then clusters the sequences using a modified mBed distance method and k-means clustering. Finally, it generates the multiple sequence alignment using the HHAlign package, which aligns profile HMMs built from the sequences. Clustal Omega is widely considered one of the fastest online multiple sequence alignment tools.
The document discusses protein-protein interactions (PPIs), including an introduction to PPIs, the types of interactions, techniques used to study them like X-ray crystallography, NMR spectroscopy and cryo-electron microscopy, and factors that affect PPIs. It also covers methods to investigate PPIs such as affinity purification coupled with mass spectrometry and yeast two-hybrid screening. Applications of understanding PPIs include developing therapeutic drugs and identifying functions of unknown proteins.
Protein databases contain information on protein sequences, structures, and functions. The major protein databases are:
- Protein Data Bank (PDB) which contains 3D protein structures determined via X-ray crystallography or NMR.
- Swiss-Prot which contains manually annotated protein sequences and functions.
- TrEMBL which supplements Swiss-Prot with automatically annotated translations of DNA sequences.
Protein databases are important for comparing proteins, understanding relationships between proteins, and aiding the study of new proteins. Searching databases is often the first step in protein research.
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.
The document summarizes a research paper that studied the incoherent feed forward loop (I1-FFL) network motif in the galactose system of E. coli. It found that the I1-FFL accelerates the response time of the galE gene to depletion of glucose by allowing initial rapid expression from CRP activation before repression by GalS occurs. The galE promoter dynamics showed an accelerated response and overshoot not seen in the simple lacZ promoter regulation. Deletion of the GalS binding site eliminated this accelerated response, demonstrating it is dependent on the I1-FFL structure.
Homology modeling, also known as comparative modeling of protein, refers to constructing an atomic-resolution model of the "target" protein from its amino acid sequence and an experimental three-dimensional structure of a related homologous protein.
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.
This document discusses motifs, which are nucleotide or amino acid sequence patterns associated with biological functions. It defines motifs, patterns, and profiles. Motifs are conserved regions, patterns are qualitative expressions, and profiles are quantitative representations. It discusses tools for de novo prediction of motifs like MEME and resources for motif discovery. Finally, it provides examples of motifs, patterns, and building position specific scoring matrices from sample sequences.
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
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.
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.
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
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
Bioinformatic tools can be applied throughout the drug design process to reduce costs and time. High-throughput screening allows testing of millions of compounds against protein targets. Computer modeling predicts compound activity and allows virtual screening. Molecular modeling visualizes compound-protein interactions to understand mechanisms of action. In silico models predict absorption, distribution, metabolism, and excretion to evaluate drug properties without animal testing. Bioinformatics databases provide protein and compound structure information to inform drug target and lead identification. Together these tools automate and accelerate key steps in drug design and development.
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 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.
ESTs are short sequences of DNA that represent genes expressed in certain tissues or organisms. They provide a quick and inexpensive way for scientists to discover new genes and map their positions in genomes. ESTs represent a snapshot of genes expressed in a tissue at a given time. Sequencing the beginning or end of cDNA clones produces 5' and 3' ESTs, which can help identify genes and study gene expression and regulation.
Proteins : is made of chain of amino acids ( amino acid= monomers) therefor the protein is polymers .
The proteins are made up of carbon, hydrogen, oxygen, and nitrogen.
Amino acid :
The document discusses Ramachandran plots, which are used to visualize allowed regions of dihedral angles phi and psi in protein backbone structures. Ramachandran plots show amino acid residues as dots in a two-dimensional map based on their phi and psi angles. Most residues cluster in favored regions corresponding to alpha helices and beta sheets. The document outlines how Ramachandran plots are constructed and analyzed using various software, and their applications in validating protein structures and understanding relationships between structure and amino acid sequence.
This document discusses motifs and domains in proteins. It defines motifs as short conserved regions related to function, such as binding sites, that are not detectable by sequence searches. There are sequence motifs consisting of nucleotide or amino acid patterns, and structural motifs formed by amino acid spatial arrangements. Domains are stable, independently folding units of proteins that determine structure and function. Both motifs and domains are useful for classifying protein families and have structural and functional roles, though domains are more stable independently. Motifs and domains form through interactions of alpha helices and beta sheets and have similarities, but domains mainly determine unique functions while motifs mainly provide structural roles within families.
Clustal Omega is a fast and scalable program for multiple sequence alignment. It begins by producing pairwise alignments using a word-based heuristic method. It then clusters the sequences using a modified mBed distance method and k-means clustering. Finally, it generates the multiple sequence alignment using the HHAlign package, which aligns profile HMMs built from the sequences. Clustal Omega is widely considered one of the fastest online multiple sequence alignment tools.
The document discusses protein-protein interactions (PPIs), including an introduction to PPIs, the types of interactions, techniques used to study them like X-ray crystallography, NMR spectroscopy and cryo-electron microscopy, and factors that affect PPIs. It also covers methods to investigate PPIs such as affinity purification coupled with mass spectrometry and yeast two-hybrid screening. Applications of understanding PPIs include developing therapeutic drugs and identifying functions of unknown proteins.
Protein databases contain information on protein sequences, structures, and functions. The major protein databases are:
- Protein Data Bank (PDB) which contains 3D protein structures determined via X-ray crystallography or NMR.
- Swiss-Prot which contains manually annotated protein sequences and functions.
- TrEMBL which supplements Swiss-Prot with automatically annotated translations of DNA sequences.
Protein databases are important for comparing proteins, understanding relationships between proteins, and aiding the study of new proteins. Searching databases is often the first step in protein research.
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.
The document summarizes a research paper that studied the incoherent feed forward loop (I1-FFL) network motif in the galactose system of E. coli. It found that the I1-FFL accelerates the response time of the galE gene to depletion of glucose by allowing initial rapid expression from CRP activation before repression by GalS occurs. The galE promoter dynamics showed an accelerated response and overshoot not seen in the simple lacZ promoter regulation. Deletion of the GalS binding site eliminated this accelerated response, demonstrating it is dependent on the I1-FFL structure.
This document discusses the creation of M-Coalition, a regional network of organizations advocating for the rights of men who have sex with men (MSM) in the Middle East and North Africa. It began in January 2014 when activists from 5 Arab countries met in Lebanon and established the coalition. A second meeting in May 2014 formed a steering committee and strategic plan with partners like UNAIDS. The coalition aims to ensure an effective response to the rising HIV epidemic among MSM through advocacy, information sharing, research, networking and capacity building. Its official launch was in 2014 and it works to meaningfully involve MSM and people living with HIV at all levels.
1) The study tested ways to reduce neophobia in goats when encountering unfamiliar feeds. In Experiment 1, goats were more willing to eat rice straw when it was offered with the odor or flavor of familiar grasses, taking 4 days, rather than 10 days without cues or 20 days with an unpleasant odor.
2) Experiment 2 found that goats exposed to rice straw or bran before weaning with their mothers or other goats immediately ate them after weaning, unlike goats without prior exposure who took over 7 days.
3) The results suggest adding familiar cues or social learning from elders can help goats more quickly accept unfamiliar feeds, which may improve production when diets frequently change.
This document presents a proposal for an anaerobic digestion system to process food waste from Clemson University's dining halls. It estimates that 262.5 tons of food waste is produced annually that could be used to produce biogas through anaerobic digestion. The goals of the project are to destroy 60% of volatile solids and produce 70% of the theoretical methane yield from the food waste. The document discusses governing equations, preliminary data collection, system design considerations, energy output estimates, and sustainability measures for the proposed anaerobic digestion system.
This document provides an introduction and overview to a course on business ethics. It discusses the course aims, format, assessment, and topics that will be covered. These include major ethical theories like deontology, utilitarianism and virtue ethics. It also provides background on the history and development of business ethics as a field of study, noting it emerged in the 1970s in response to criticism of corporate social responsibility. The role of business ethics today is to help students and professionals evaluate complex ethical issues that arise in business but may not be addressed by other areas of study or work experience.
The document analyzes the genre, target audience, and visual elements of a magazine contents page and front cover. It finds that the magazine, called KERRANG!, targets a rough, rebellious audience as shown through images of band members with long hair and beards. The color scheme is black and white to convey anarchy and going against mainstream culture. Text layout and design elements like the cracked glass logo are also analyzed in terms of representing the magazine's genre and intended readers.
This document contains the final examination timetable for the first semester of the 2014/2015 academic year at Kampus Putrajaya. It lists the course codes, course names, number of candidates, and venues for examinations taking place from September 15-20, 2014. Examinations are scheduled from 9am-12pm and 2:30-5:30pm on weekdays, and from 9am-12pm and 2:30-5:30pm on Saturdays across multiple venues including the Library Hall and Dewan Seri Sarjana. Over 50 examinations are scheduled during this period covering a wide range of subjects.
1. The document provides a draft examination programme for the FE to BE examinations to be held in December 2014 at Shivaji University, Kolhapur.
2. It lists the examination dates and subjects for FE semester I and II (new and old syllabus), as well as SE semester III (new and old syllabus) for all branches.
3. It also provides information on examination centers and instructions for candidates and colleges.
The Puget Restoration Project involves a team of four people - Karris, Jessica, Will, and Ethan - working on a site restoration. The document lists the names of the team members working on the Puget Restoration Project and provides the heading "Site Location" but no further details about the location.
X-ray crystallography is a technique used to determine the three-dimensional atomic structure of crystals. X-rays are diffracted by the crystal and the diffraction pattern is collected on a detector. By analyzing the diffraction pattern using Bragg's law and Fourier transforms, scientists can construct electron density maps and refine protein structures at high resolution. Key aspects of X-ray crystallography include generating X-rays, collecting diffraction data, solving protein structures, and refining models using computational methods. This technique has provided atomic level insights into protein structure and been instrumental in numerous scientific discoveries through applications like determining unknown material structures.
This document describes the "Wings" app, which teaches multiplication through a game where students steer a bird to the greater number or product, rather than just memorizing facts. The app has different levels that can be upgraded, including pre-multiplication, basic multiplication, and advanced multiplication, with individual levels costing $2.99-$3.99 or all levels together for $6.99.
This document proposes designing an anaerobic digestion system to process food waste from Clemson University's dining halls. Over 300 tons of food waste is produced annually. An anaerobic digester would allow the waste to be converted into biogas, primarily methane, which could be used to generate electricity and reduce Clemson's reliance on non-renewable energy. The proposed design involves sizing a continuous stirred-tank reactor to handle food waste and paper inputs. Calculations are shown to determine reactor volume, mixing requirements, heating needs, and estimated biogas and energy yields from the system. Safety measures for the reactor are also outlined.
Tool steels are specialized alloy steels designed for tooling applications that require high strength and hardness. There are several types of tool steel including shock-resisting, cold-worked, hot-worked, high-speed, and water-hardened steels, each suited for different applications like cutting, forming, or stamping. Cast irons like grey, white, ductile, and malleable iron are also discussed, outlining their compositions and common uses.
This document provides an overview of Puget Sound restoration efforts, focusing on estuaries, deltas, beaches and bluffs. It discusses the productivity of estuaries but also the degradation issues they face from pollution, overfishing and poor land management practices. The Nooksack River Delta restoration project aims to remove levees and dikes that disrupt natural water flows, restoring tidal channels and floodplains to improve conditions for fish and wildlife. The Lilliwaup Estuary project replaced a causeway and restored estuary processes to benefit local ecology. Puget Sound restoration addresses improving natural conditions across different habitat types to enhance the overall health of the sound.
protein design, principles and examples.pptxGopiChand121
Protein design uses structural biology knowledge to predict amino acid sequences that produce proteins with targeted properties, allowing hypotheses to be tested. Computational methods now design proteins very different from known ones. Protein design remains an important problem, and current methods largely use physics-based approaches relying on single structures, despite multiple structures being available. A new method called FlexiBaL-GP uses machine learning to learn lower dimensional representations of backbone movements from multiple structures.
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.
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.
The document discusses protein structure prediction methods such as homology modeling and threading. Homology modeling relies on sequence similarity between the target and template proteins to generate a structural model. It involves aligning the sequences, building the backbone based on the template, and modeling side chains. Threading methods can be used when sequence similarity is low but still detects structural similarity by identifying conserved protein folds from structural databases. Experimental techniques like X-ray crystallography and NMR spectroscopy determine protein structures but have limitations for some proteins.
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.
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.
This document discusses protein structure prediction and molecular modeling. It begins with an overview of the druggable genome and protein structure prediction approaches such as ab initio modeling, threading, and homology modeling. It then provides details on homology modeling steps including searching databases, selecting templates, aligning sequences, building models, and model evaluation. The document also discusses protein-ligand docking, scoring functions, assessing docking performance, and practical aspects of docking such as protein and ligand preparation.
The document discusses using cloud computing for protein structure prediction and gene expression data analysis. Protein structure prediction is a computationally intensive task that helps design new drugs, but determining protein structures manually is difficult. Cloud computing enables scientists to submit protein structure prediction tasks to a cloud service without worrying about the complex predictions. It also discusses using gene expression profiling and classification algorithms like eXtended Classifier System (XCS) on cloud infrastructure to analyze large cancer and medical diagnosis datasets.
Cloud applications - Protein Structure Predication and gene expression data...Pushpendra Singh Dangi
This document discusses using cloud computing for protein structure prediction and gene expression data analysis. Protein structure prediction is a computationally intensive task that determines the 3D structure of proteins from their amino acid sequences. Cloud computing allows this task to be parallelized across multiple machines to reduce computational time. Gene expression profiling measures thousands of genes and is used for cancer prediction and diagnosis. Analyzing large gene expression datasets for cancer classification is solved using an extended classifier system on cloud infrastructure to further divide and parallelize the problem.
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
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.
(1) There are four levels of protein structure: primary, secondary, tertiary, and quaternary. Experimental methods like X-ray crystallography and NMR spectroscopy can determine protein structures but are expensive and time-consuming. (2) Computational structure prediction methods include homology/comparative modeling, protein threading, and ab initio modeling. Homology modeling is most reliable when the sequence identity is over 30-50% to a template with a known structure. (3) Protein threading is used when there is no clear homolog but the protein may have the same fold as one in PDB. It aligns sequences to structures and evaluates fitness to predict the model.
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.
Homology modeling is a computational technique for predicting the structure of a protein target based on its sequence similarity to proteins with known structures, and it involves finding a suitable template, aligning the target and template sequences, building a 3D model of the target, and evaluating the model quality. While experimental methods like X-ray crystallography and NMR can determine protein structures, they have limitations in terms of which proteins can be studied, so computational methods like homology modeling are needed to predict structures for the many proteins whose structures remain unknown.
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 ...
This document provides an overview of protein structure prediction. It begins by defining the primary, secondary, and tertiary protein structures. It then discusses how to predict secondary structures using servers like PSIPRED and features like transmembrane domains. Next, it covers retrieving protein structures from the PDB and using BLAST and homology modeling to predict structures for proteins without known structures. It concludes by noting the challenges in predicting protein movements and interactions.
Combanitorial approach for drug discoveryShwetA Kumari
Combinatorial chemistry is a new approach to drug discovery that involves synthesizing and testing large libraries of compounds in parallel rather than one by one. This allows for more rapid and cost-effective discovery of potential drug leads. There are two main challenges in drug discovery that combinatorial chemistry addresses: identifying a lead compound with the desired biological activity, and optimizing the lead compound. Solid phase synthesis and solution phase synthesis are two main combinatorial methods. Case studies demonstrate how combinatorial synthesis approaches have been used to develop inhibitors of influenza endonuclease, kinase inhibitors, and modulators of orexin receptors.
This document provides an overview of protein kinase cascades. It begins with an introduction to protein kinases and their function in phosphorylating proteins and playing roles in cellular processes. It then discusses the classification of protein kinases based on the amino acid they phosphorylate. Next, it explains the basic mechanism of phosphorylation by protein kinases using ATP. It proceeds to describe protein kinase cascades where one kinase phosphorylates and activates the next in a series. Examples of double phosphorylation and multi-layer perceptrons in cascades are illustrated. Finally, some biological examples of different types of protein kinases are mentioned before concluding with references.
This document provides an introduction and overview of data mining. It discusses how data mining extracts knowledge from large amounts of data to discover hidden patterns and predict future trends. It notes that for effective data mining, data sets need to be extremely large. The document outlines some key techniques of data mining including associative learning, artificial neural networks, clustering, genetic algorithms, and hidden Markov models. It also discusses applications of data mining in bioinformatics such as gene finding, protein function prediction, and disease diagnosis. Finally, it acknowledges that while bioinformatics data is rich, developing comprehensive theories remains challenging but creates opportunities for novel knowledge discovery methods.
paper ppt 2ndry str in globular proteinShwetA Kumari
This paper presents a method for predicting the secondary structure of globular proteins from their amino acid composition. The researchers analyzed data from 18 proteins with known sequences and structures to develop regression models correlating amino acid percentages with helix, sheet, turn and coil content. They achieved average errors of 7.1% for helix, 6.9% for sheet, 4.2% for turn and 5.7% for coil predictions on these proteins. A second model was also provided to account for uncertainties in differentiating between amino acids. The method provides a useful way to estimate secondary structure when only amino acid composition is known.
Aminiacid Selenocysteine and PyrrolysineShwetA Kumari
This presentation summarizes the 21st and 22nd amino acids, selenocysteine and pyrrolysine. Selenocysteine contains selenium in place of sulfur and is encoded by the UGA codon. It plays an important role in antioxidant enzymes. Pyrrolysine is a recently discovered 22nd amino acid encoded by UAG codon. It contains a pyrroline ring and is used by some archaea in methane production. Both expand the genetic code beyond the standard 20 amino acids.
This document discusses dot plot analysis, which allows comparison of two biological sequences to identify similar regions. It describes how dot plots are generated using a similarity matrix and defines different features that can be observed, such as identical sequences appearing on the principal diagonal, direct and inverted repeats appearing as multiple diagonals, and low complexity regions forming boxes. Applications of dot plot analysis include identifying alignments, self-base pairing, sequence transposition, and gene locations between genomes. Limitations include high memory needs for long sequences and low efficiency for global alignments.
This document provides an overview of protein kinase cascades. It begins with an introduction to protein kinases and their function in phosphorylating proteins and playing roles in cellular processes. It then discusses the classification of protein kinases based on the amino acid they phosphorylate. Next, it explains the basic mechanism of phosphorylation by protein kinases using ATP. It proceeds to describe protein kinase cascades where one kinase phosphorylates and activates the next in a chain. Examples of double phosphorylation and multi-layer perceptrons in cascades are illustrated. Finally, some biological examples of different types of protein kinases are mentioned before concluding with references.
This document provides an overview of evolution including:
1) Darwin's theory of evolution by natural selection, where organisms change over generations through heritable traits that provide an advantage.
2) Evidence that supported Darwin's ideas like fossils showing gradual changes and biogeography patterns.
3) The mechanisms of evolution including mutation, genetic drift, migration and natural selection acting on variation between individuals.
4) Examples of evolution through changes in species like whales becoming aquatic and Darwin's finches on the Galapagos.
The document summarizes Darwin's theory of natural selection. It explains the key factors of Darwinism: rapid multiplication of organisms, limited environmental resources causing competition, variation between individuals, and survival and inheritance of beneficial traits. Through this process of natural selection over generations, species gradually change and new species may form as variations accumulate. The theory helped explain the evolution of species and adaptation to the environment. It contrasts with Lamarckism in its view of inheritance and lack of internal forces driving evolution.
Genetic drift is a mechanism of evolution that causes changes in allele frequencies in a population due to random sampling of organisms. It is common in small populations and can cause some alleles to become more common or disappear entirely over time. There are two main types of genetic drift: the bottleneck effect, which occurs when a disaster reduces population size, and the founder effect, which happens when a group founds a new population. Both types can lead to new populations becoming genetically distinct from the original population and play a role in evolution and speciation.
PPT on Direct Seeded Rice presented at the three-day 'Training and Validation Workshop on Modules of Climate Smart Agriculture (CSA) Technologies in South Asia' workshop on April 22, 2024.
ESR spectroscopy in liquid food and beverages.pptxPRIYANKA PATEL
With increasing population, people need to rely on packaged food stuffs. Packaging of food materials requires the preservation of food. There are various methods for the treatment of food to preserve them and irradiation treatment of food is one of them. It is the most common and the most harmless method for the food preservation as it does not alter the necessary micronutrients of food materials. Although irradiated food doesn’t cause any harm to the human health but still the quality assessment of food is required to provide consumers with necessary information about the food. ESR spectroscopy is the most sophisticated way to investigate the quality of the food and the free radicals induced during the processing of the food. ESR spin trapping technique is useful for the detection of highly unstable radicals in the food. The antioxidant capability of liquid food and beverages in mainly performed by spin trapping technique.
The debris of the ‘last major merger’ is dynamically youngSérgio Sacani
The Milky Way’s (MW) inner stellar halo contains an [Fe/H]-rich component with highly eccentric orbits, often referred to as the
‘last major merger.’ Hypotheses for the origin of this component include Gaia-Sausage/Enceladus (GSE), where the progenitor
collided with the MW proto-disc 8–11 Gyr ago, and the Virgo Radial Merger (VRM), where the progenitor collided with the
MW disc within the last 3 Gyr. These two scenarios make different predictions about observable structure in local phase space,
because the morphology of debris depends on how long it has had to phase mix. The recently identified phase-space folds in Gaia
DR3 have positive caustic velocities, making them fundamentally different than the phase-mixed chevrons found in simulations
at late times. Roughly 20 per cent of the stars in the prograde local stellar halo are associated with the observed caustics. Based
on a simple phase-mixing model, the observed number of caustics are consistent with a merger that occurred 1–2 Gyr ago.
We also compare the observed phase-space distribution to FIRE-2 Latte simulations of GSE-like mergers, using a quantitative
measurement of phase mixing (2D causticality). The observed local phase-space distribution best matches the simulated data
1–2 Gyr after collision, and certainly not later than 3 Gyr. This is further evidence that the progenitor of the ‘last major merger’
did not collide with the MW proto-disc at early times, as is thought for the GSE, but instead collided with the MW disc within
the last few Gyr, consistent with the body of work surrounding the VRM.
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.
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.
(June 12, 2024) Webinar: Development of PET theranostics targeting the molecu...Scintica Instrumentation
Targeting Hsp90 and its pathogen Orthologs with Tethered Inhibitors as a Diagnostic and Therapeutic Strategy for cancer and infectious diseases with Dr. Timothy Haystead.
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
Mending Clothing to Support Sustainable Fashion_CIMaR 2024.pdfSelcen Ozturkcan
Ozturkcan, S., Berndt, A., & Angelakis, A. (2024). Mending clothing to support sustainable fashion. Presented at the 31st Annual Conference by the Consortium for International Marketing Research (CIMaR), 10-13 Jun 2024, University of Gävle, Sweden.
The technology uses reclaimed CO₂ as the dyeing medium in a closed loop process. When pressurized, CO₂ becomes supercritical (SC-CO₂). In this state CO₂ has a very high solvent power, allowing the dye to dissolve easily.
1. 1
Central University of Bihar
BIS 553: protein modelling and simulation
Denovo structure prediction
Submitted to:- Submitted by:-
Dr. Durg Vijay Singh Shweta Kumari
Roll no- 21
2 nd semester
Central University of Bihar
Patna
2. 2
CONTENT
Sl. No Topic Page No.
1 Introduction 3
2 Need of Ab inito prediction 4
3 Challenges 4
4 Principle of ab inito method 4
5 Denovo Structure Prediction V/S Template
Based Structure Prediction
4-5
6 Successful De Novo Modeling Requirements 6
7 Results from abinitio 7
8 Domain prediction 7-8
9 Advantages of This Method 8-9
10 Complexity of abinitio methods 9
11 Ab initio methods have recently received
increased attention in the prediction of loops
10
12 Protein folding and de novo protein design for
biotechnological applications
10
13 Limitations of De novo Prediction Methods 11
14 CASPs 11-12
15 Application of Denovo structure prediction 12
16 List of de novo protein structure prediction
software
12-13
17 References 14
3. 3
Introduction:
Predicting the 3D structure without any “prior
knowledge”
•Predicting protein 3D structures from the amino acid sequence still remains
as an unsolved problem after five decades of efforts. If the target protein has a
homologue already solved, the task is relatively easy and high-resolution
models can be built by copying the framework of the solved structure.
•However, such a modelling procedure does not help answer the question of
how and why a protein adopts its specific structure. If structure homologues
(occasionally analogues) do not exist, or exist but cannot be identified, models
have to be constructed from scratch. This procedure, called ab initio
modelling.
•Ab initio modelling is essential for a complete solution to the protein
structure prediction problem; it can also help us understand the
physicochemical principle of how proteins fold in nature.
Thus,” In computational biology, de novo protein structure prediction refers to an
algorithmic process by which protein tertiary structure is predicted from its
amino acid primary sequence.”
4. 4
Need of Ab inito prediction:
• First, in some cases, even a remotely related structural homologue may not be
available.
• Second, new structure continue to be discovered which could not have been
identified by methods which rely on comparison to known structure.
• Third, knowledgebased methods have been criticized for predicting protein
protein structures without having to obtain a fundamental understanding of the
mechanisms and driving forces of structure formation. Ab initio methods, in
contrast, base their predictions on physical models for these mechanisms
Challenges:
• Energy functions that can reliable discriminat e native and nonnative
structures.
• Enormous amount of computations.
Principle of ab inito method:
•It is based on the ‘thermodynamic hypothesis’, which states that the native
structure of a protein is the one for which the free energy achieves the global
minimum.
•ANFINSEN (1973) showed that all the information necessary for a protein to fold
to the native state residue in the protein sequence.
•In the absence of large kinetic barriers in the force energy landscape, Anfinsen's
result and those of large numbers of researchers in the intervening year suggest that
the native confoermations of most proteins are the lowest free energy conformation
for their sequences.
Denovo Structure Prediction V/S Template Based
Structure Prediction:
•De novo protein structure modeling is distinguished from Template-based
modeling (TBM) by the fact that no solved homolog to the protein of interest is
known, making efforts to predict protein structure from amino acid sequence
exceedingly difficult.
5. 5
Sl.
No.
Homology
modelling
Fold Reconition De novo
prediction
1 templete based
modelling
templete based remote
homology modelling
templete free
modelling
2 applicable to sequence
having >= 30% homogy
on PDB database
applicable to sequence
having <20% homogy on
PDB database
applicable to any
sequence does not
having homologue
on PDB
3 length of sequence is not
limited
greater than 150AA
not applicable
4 limited search space search space greater than
homology modelling
very large search
space
5 more accurate structure generate less accurate
structure than homology
generate least
accurate structure
6 model quality at atomic
level
model quality at fold level model quality at
atomic level
7 computationally less
expensive
computationally more
expensive than homology
modelling
computationally
most expensive
8 applicable in Drug
designing, virtual
screening, designing site
directed mutagenisis,
characterization of active
site
applicable in Prediction of
protein family, functional
characterization by folding
assignment
applicable in
genome annotation,
domain prediction
and structural
genomics initiatives
7. 7
Results from abinitio:
•Average error 5 Å -Average error 5 Å - 10 Å10 Å
•Function cannot beFunction cannot be predictedpredicted
••Long simulationsLong simulations
fig:fig: Some protein from ESome protein from E.coli.coli predicted at 7.6 Åpredicted at 7.6 Å
(CASP3, H.Scheraga)(CASP3, H.Scheraga)
Domain prediction:
•Domain prediction is a critical pre resquisite to the structur prediction “As the size of
the protein increases, its conformational space also increases.”
•Current denovo methods are limited to protein domain of 150 amino acid domain
residue for alpha-beta protein.
•80 residue for beta folds and 150 for alpha fold only.
•To overcome this two approaches can apply-
1. Increase the size range of denovo structure prediction.
2. Dividing protein into domains prior to attempting two protein structure
prediction.
•"A domain is generally define as a portion of protein that folds independently of the
rest of the protein."
•So dividing a query sequence into their smallest component domain prior to folding
is straight forward way to increase the size of the predictio.
•For many proteins domains division can be easily found while several domain
remains beyond our ability to correctly detached them.
•The determination of domain, family membership and its boundries for multidomain
protein is a vital step in structure annotation/ prediction.
•In brief, most domain protein partial methods relay on hierarchy searching for
domains in query sequence with collection of primary sequence methods, domains
library search and matches to structural domains in the PDB.
8. 8
Advantages of This Method:
•The method is fully automated, and the methodology is the same regardless of the
existing homology between the query protein and the proteins in the structural
database. Thus, it can be easily applied to the structural annotation on a genomic
scale.
•A large success rate, which is competitive with other methods (a large fraction of
correct and accurate predictions), could be expected for the following types of
proteins.
The most advanced abinitio method is fragment assembly
•Consists by breaking up the sequence in small subsegments of 3 to 9 residues and
generating structure for these segments based on a large library of known fragments.
•Decoys are generated from all possible combinations of fragments.
•An energy minimization process is applied to all decoys.
10. 10
Ab initio methods have recently received increased
attention in the prediction of loops:
•Loops exhibit greater structural variability than Beta-sheets and Alpha helices.
•Loop structure therefore is considerably more difficult to predict than the structure
of the geometrically highly regular Beta-sheets and Alpha helices.
•Loops are often exposed to the surface of proteins and contribute to active and binding sites.
Consequently, loops are crucial for protein function.
Protein folding and de novo protein design for
biotechnological applications:
Advances and challenges in the fields of protein structure prediction and de novo
protein design focusing on the interplay necessary for success. schematically shows
the roadmap and key challenges in protein structure prediction and de novo protein
design. The past few years have shown impressive applications of computational
structure prediction and design to biotechnology, spanning peptide or antibody
therapeutics, novel biocatalysts, and self-assembling nanomaterials.
Fig: Roadmap of key challenges in understanding how to predict protein sequence to structure to
function and design. Structure prediction begins with a primary amino acid sequence
11. 11
Table. Summary of recent successful computational de novo designed and
redesigned systems and their biotechnological applications
source: http://www.sciencedirect.com/science/article/pii/S0167779913002266#
Limitations of De novo Prediction Methods:
•Pure abinitio modelling is still very costly and ineffective but hybrid
homology/ab initio methods such as fragment assembly have better performance
•A major limitation of de novo protein prediction methods is the extraordinary
amount of computer time required to successfully solve for the native confirmation of
a protein.
•Distributed methods, such as Rosetta@home, have attempted to ameliorate this by
recruiting individuals who then volunteer idle home computer time in order to
process data.
•Even these methods face challenges, however. For example, a distributed method
was utilized by a team of researchers at the University of Washington and the
Howard Hughes Medical Institute to predict the tertiary structure of the protein
T0283 from its amino acid sequence. In a blind test comparing the accuracy of this
distributed technique with the experimentally confirmed structure deposited within
the Protein Databank (PDB), the predictor produced excellent agreement with the
deposited structure.
•However, the time and number of computers required for this feat was enormous –
almost two years and approximately 70,000 home computers, respectively.
“One method proposed to overcome such limitations involves the use of Markov
models (see Markov chain Monte Carlo). One possibility is that such models could
be constructed in order to assist with free energy computation and protein
structure prediction, perhaps by refining computational simulations”
CASPs:
•“Progress for all variants of computational protein structure prediction methods is
assessed in the biannual, community wide Critical Assessment of Protein Structure
Prediction (CASP) experiments.
12. 12
•To assess the current status of protein structure prediction, John Moult proposed the
CASP (Critical Assessment of Techniques for Protein Structure Prediction)
communitywide protein structure prediction experiment.
•The idea is that experimentalists who are about to determine protein structures make
the sequences of the proteins available and then the protein structure prediction
community makes predictions that are then assessed by independent reviewers.
•Attendees tested recently developed ab initio protein structure predictions methods
during the CASP3 exercises, conducted in December 1998 in Asilomar, California.
•Among the best performing ab initio methods was the Rosetta method developed by
David Baker and coworkers.
Application of Denovo structure prediction:
Genome functional annotation and structure genomics initiate two areas of
research where ab initio protein structured prediction could take important
contributions.
1. Genome annotation:
a. The annotation of open reading frames lacking detectable sequence homology to protein of
known function represents a promising applicable for ab initio model.
Low resolution ab initio predicted structure and functional relationships between proteins not
apparent from sequence similarity alone.
Note:- This concept is well illustrated by some example of prediction from CASP4.
b. Ab initio structure could be probed for the presense of residue adopting conserved geometric
motifs (eg. Serin protease catalysis traids).
2) structural genomics initiatives:
a) an initio structure prediction can help guide target selection by focussing experimental structure
determination on those proteins likely to adopt novel folds or to be of particular biological
importance
b) an initio technique do not face the limitations which comes in homology modelling applied on
genomic scale ( need for at least one homologue of known structure with good coverage).
Thus, may be a valuable adjunct to homology methods, filling in structural gaps and
producing much more complete set of model.
13. 13
List of de novo protein structure prediction
software:
Name Method Description Link
EVfold
Evolutionary couplings calculated from correlated
mutations in a protein family, used to predict 3D
structure from sequences alone and to predict
functional residues from coupling strengths. Predicts
both globular and transmembrane proteins.
Webserver
http://evfold
.org/evfold-
web/evfold.
do
QUARK Monte Carlo fragment assembly
On-line server for
protein modeling (best
for ab initio folding in
CASP9)
http://zhang
lab.ccmb.m
ed.umich.ed
u/QUARK/
NovaFold Combination of threading and ab initio folding
Commercial protein
structure prediction
application
http://www.
dnastar.com
/t-products-
NovaFold.a
spx
I-TASSER Threading fragment structure reassembly
On-line server for
protein modeling
http://zhang
lab.ccmb.m
ed.umich.ed
u/I-
TASSER/
Selvita Protein
Modeling Platform
Package of tools for protein modeling
Interactive webserver
and standalone program
including: CABS ab
initio modeling
http://www.
selvita.com/
selvita-
protein-
modeling-
platform.ht
ml
ROBETTA
Rosetta homology modeling and ab initio fragment
assembly with Ginzu domain prediction
Webserver
http://www.
robetta.org/
Rosetta@home
Distributed-computing implementation of Rosetta
algorithm
Downloadable program
http://boinc.
bakerlab.org
/rosetta/
CABS Reduced modeling tool Downloadable program
CABS-FOLD
Server for de novo modeling, can also use alternative
templates (consensus modeling).
Webserver
http://bioco
mp.chem.u
w.edu.pl/C
ABSfold/
Bhageerath
A computational protocol for modeling and
predicting protein structures at the atomic level.
Webserver
http://www.
scfbio-
iitd.res.in/b
hageerath/in
dex.jsp
Abalone Molecular Dynamics folding Program
PEP-FOLD
De novo approach, based on a HMM structural
alphabet
On-line server for
peptide structure
prediction
http://bioser
v.rpbs.univ-
paris-
diderot.fr/se
rvices/PEP-
FOLD/