molecular docking its types and de novo drug design and application and softw...GAUTAM KHUNE
This ppt deals with all the aspects related to molecular docking ,its types(rigid ,flexible and manual) and screening based on it and also deals with de novo drug design , various softwares available for docking methodologies and applications for molecular docking in new drug design
Drug discovery take years to decade for discovering a new drug and very costly
Effort to cut down the research timeline and cost by reducing wet-lab experiment use computer modeling
Others have done the work. Some have used the work. I have spoken only on behalf of their behalf.
molecular docking its types and de novo drug design and application and softw...GAUTAM KHUNE
This ppt deals with all the aspects related to molecular docking ,its types(rigid ,flexible and manual) and screening based on it and also deals with de novo drug design , various softwares available for docking methodologies and applications for molecular docking in new drug design
Drug discovery take years to decade for discovering a new drug and very costly
Effort to cut down the research timeline and cost by reducing wet-lab experiment use computer modeling
Others have done the work. Some have used the work. I have spoken only on behalf of their behalf.
In silico drug designing is the drug design which can be carried out in silicon chip,i.e., within computers. The slides are helpful to know a brief description about in silico drug designing.
In silico drug designing is the drug design which can be carried out in silicon chip,i.e., within computers. The slides are helpful to know a brief description about in silico drug designing.
PRESENTED BY: HARSHPAL SINGH WAHI, SHIKHA D. POPALI
USEFUL FOR PHARMACY STUDENTS AND ACADEMICS, INDUSTRIALS FOR MOLECULE DEVELOPMENT, MODELING, DRUG DISCOVERY, COMPUTATIONAL TOOLS, MOLECULAR DOCKING ITS TYPES, FACTORS AFFECTING, DIFFERENT STAGES, QSAR ADVANTAGES, NEED
Hey students here i am attaching the powerpoint presenatation on the Receptor/enzyme-interaction and its analysis, Receptor/enzyme cavity size prediction, predicting
the functional components of cavities and the concept regarding the fragment based drug design.
1. Scoring functions are the mathematical functions used to approximately predict the binding affinity between two molecules after they have been docked.
The evaluation and ranking of predicted ligand conformations is a crucial aspect of structure-based virtual screening.
2. Scoring functions implemented in docking programs make simplifications in the evaluation of modeled complexes.
3. Affinity scoring functions are applied to the energetically best pose found for each molecule, and comparing the affinity scores for different molecules gives their relative rank-ordering.
Review on Computational Bioinformatics and Molecular Modelling Novel Tool for...ijtsrd
Advancement in science and technology has brought a remarkable change in the field of drug discovery. Earlier it was very difficult to predict the target for receptor but nowadays, it is easy and robust task to dock the target protein with ligand and binding affinity is calculated. Docking helps in the virtual screening of drug along with its hit identification. There are two approaches through which docking can be carried out, shape complementary and stimulation approach. There are many procedures involved in carrying out docking and all require different software's and algorithms. Molecular docking serves as a good platform to screen a large number of ligands and is useful in Drug-DNA studies. This review mainly focuses on the general idea of molecular docking and discusses its major applications, different types of interaction involved and types of docking. Rishabh Jain "Review on Computational Bioinformatics and Molecular Modelling: Novel Tool for Drug Discovery" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-1 , December 2018, URL: http://www.ijtsrd.com/papers/ijtsrd18914.pdf
http://www.ijtsrd.com/pharmacy/pharmacoinformatics/18914/review-on-computational-bioinformatics-and-molecular-modelling-novel-tool-for-drug-discovery/rishabh-jain
Important Interaction in Drug Receptor Complex And Intro to De Novo Drug Desi...Yogesh Chaudhari
#Important Interaction in Drug Receptor Complex And Intro to De Novo Drug Design
Its includes all the interaction like covalent and non covalent interaction like ionic (electrostatic) interactions,
ion-dipole and dipole-dipole interactions,
Hydrogen bonding,
Charge-transfer interactions,
Hydrophobic interactions,
Halogen bonding,
Vander Waals interactions. And introduction to de novo dug design which includes the procedure for LUDI Softwares and other vavity site prediction.
Stable Drug Designing by Minimizing Drug Protein Interaction Energy Using PSO csandit
Each and every biological function in living organism happens as a result of protein-protein interactions. The diseases are no exception to this. Identifying one or more proteins for a
particular disease and then designing a suitable chemical compound (known as drug) to destroy these proteins has been an interesting topic of research in bio-informatics. In previous methods,drugs were designed using only seven chemical components and were represented as a fixedlength
tree. But in reality, a drug contains many chemical groups collectively known as
pharmacophore. Moreover, the chemical length of the drug cannot be determined before
designing the drug.
In the present work, a Particle Swarm Optimization (PSO) based methodology has been
proposed to find out a suitable drug for a particular disease so that the drug-protein interaction
becomes stable. In the proposed algorithm, the drug is represented as a variable length tree and essential functional groups are arranged in different positions of that drug. Finally, the structure of the drug is obtained and its docking energy is minimized simultaneously. Also, the
orientation of chemical groups in the drug is tested so that it can bind to a particular active site of a target protein and the drug fits well inside the active site of target protein. Here, several inter-molecular forces have been considered for accuracy of the docking energy. Results showthat PSO performs better than the earlier methods.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
2. Docking is a structure-based technique which attempts
to find the “best” match, between two molecules.
3. WHAT IS MOLECULAR DOCKING????
• In the field of molecular modeling, docking is a method which predicts
the preferred orientation of one molecule to a second when bound to
each other to form a stable complex.
• Knowledge of the preferred orientation in turn may be used to predict
the strength of association or binding affinity between two molecules
using for example scoring functions.
RECEPTOR LIGAND
LIGAND-RECEPTOR
COMPLEX
4. WHY IS DOCKING IMPORTANT?
Signal Transduction :- The associations between biologically relevant molecules such
as proteins, nucleic acids, carbohydrates, and lipids play a central role in signal
transduction. Furthermore, the relative orientation of the two interacting partners may
affect the type of signal produced (e.g., agonism vs antagonism). Therefore docking is
useful for predicting both the strength and type of signal produced.
Drug-Designing:- Docking is frequently used to predict the binding orientation
of small molecule drug candidates to their protein targets in order to in turn predict
the affinity and activity of the small molecule. Hence docking plays an important role in
the rational design of drugs.
5. Receptor or host or lock: The "receiving" molecule, most commonly a protein or other
biopolymer.
Ligand or guest or key: The complementary partner molecule which binds to the receptor.
Ligands are most often small molecules but could also be another biopolymer.
Docking: Computational simulation of a candidate ligand binding to a receptor.
Binding mode: The orientation of the ligand relative to the receptor as well as the
conformation of the ligand and receptor when bound to each other.
Pose : A candidate binding mode.
Scoring : The process of evaluating a particular pose by counting the number of favorable
intermolecular interactions such as hydrogen bonds and hydrophobic contacts.
Ranking : The process of classifying which ligands are most likely to interact favorably to a
particular receptor based on the predicted free-energy of binding.
DOCKING GLOSSARY
6.
7. DEFINITION OF THE PROBLEM
One can think of molecular docking as a problem of “lock-and-key”, in which one
wants to find the correct relative orientation of the “key” which will open up
the “lock” (where on the surface of the lock is the key hole, which direction to turn the
key after it is inserted, etc.)
However, since both the ligand and the protein are flexible, a “hand-in-
glove” analogy is more appropriate than “lock-and-key”. During the course of the
docking process, the ligand and the protein adjust their conformation to achieve an
overall "best-fit" and this kind of conformational adjustment resulting in the overall
binding is referred to as "induced-fit“.
8. DOCKING APPROACHES
SHAPE COMPLEMENTARITY:- One approach uses a matching technique that
describes the protein and the ligand as complementary surfaces.
SIMULATION:- The second approach simulates the actual docking process in which
the ligand-protein pairwise interaction energies are calculated. Both approaches have
significant advantages as well as some limitations.
CALCULATE:-
Hydrophilic and hydrophobic
interactions.
Hydrogen bond donated.
Hydrogen bond accepted.
Ligand orientation with best
complementarity score.
Binding affinities.
Ionic interaction.
Aromatic Interaction.
Vander Waals’ forces
Electrostatic forces
Free energies.
9. STEPS OF DOCKING
Step 1: Start with Crystal Co-ordinates with target receptor.
For example,
-HIV-1 protease is the target receptor
- Aspartyl groups are its active sites
11. Step 3: Generate spheres to fill the active site of the
receptor: The spheres become potential locations for ligand
atoms.
12. Step 4: Sphere centres are then matched with the
ligand atoms, to determine possible orientations for the
ligand.
Three scoring schemes:
o Shape scoring,
o Electrostatic scoring and
o Force-field scoring.
Step 5: Find the top scoring or the best ranking.
13. APPLICATIONS OF MOLECULAR DOCKING
Determination of the lowest free energy structures for the receptor-ligand
complex.
Calculate the differential binding of a ligand to two different macromolecular
receptors.
Study the geometry of a particular complex.
Propose modification of lead molecules to optimize potency or other properties.
De novo design for lead generation.
Library design.
Screening for the side effects that can be caused by interactions with other
molecules.
To check the specificity of the potential drug against homologous proteins
through docking.
Docking is also a widely used tool for predicting protein-protein interaction.
Knowledge of the molecular associations aid in understanding a variety of
pathways taking place in the living and in revealing of the possible pharmacological
targets.
Protein-ligand docking can also be used to predict pollutants that can be
degraded by enzymes.
15. 2. AUTODOCK- USA (1990)
AutoDock is a suite of automated docking tools. It is designed to predict how small
molecules, such as substrates or drug candidates, bind to a receptor of known 3D
structure.
Current distributions of AutoDock consist of two generations of software: AutoDock 4
and AutoDock Vina.
16. 3. FlexX- Germany (1996)
Receptor is treated as rigid.
Incremental construction algorithm:
Break Ligand up into rigid fragments
Dock fragments into pocket of receptor
Reassemble ligand from fragments.
Energy conformations
17. 4. GOLD- UK (1995)
Performs automated docking with
full acyclic ligand flexibility, partial
cyclic ligand flexibility and partial
protein flexibility in and around
active site.
Scoring: includes H-bonding term,
pairwise dispersion potential
(hydrophobic interactions),
molecular and mechanics term for
internal energy
18. OTHER SOFTWARES
AADS- India (2011)
ADAM- Japan (1994)
BetaDock- South Korea (2011)
DARWIN- USA (2000)
DIVALI- USA (1995)
DockVision- Canada (1992)
EADock- Switzerland (2007)
19. Understanding the ruling principles whereby protein receptors recognize,
interact, and associate with molecular substrates and inhibitors is of
paramount importance in drug discovery efforts. Protein-ligand docking
aims to predict and rank the structure(s) arising from the association
between a given ligand and a target protein of known 3D structure. Despite
the breathtaking advances in the field over the last decades and the
widespread application of docking methods, several downsides still exist. In
particular, protein flexibility-a critical aspect for a thorough understanding
of the principles that guide ligand binding in proteins-is a major hurdle in
current protein-ligand docking efforts that needs to be more efficiently
accounted for. In this review the key concepts of protein-ligand docking
methods are outlined, with major emphasis being given to the general
strengths and weaknesses that presently characterize this methodology.
Despite the size of the field, the principal types of search algorithms and
scoring functions are reviewed and the most popular docking tools are
briefly depicted.
CONCLUSION
20. REFERENCES
1. Lengauer T, Rarey M (1996). "Computational methods for biomolecular
docking". Curr. Opin. Struct. Biol. 6 (3): 402–6. doi:10.1016/S0959-440X(96)80061-
3. PMID 8804827
2. Jorgensen WL (1991). "Rusting of the lock and key model for protein-ligand
binding".Science 254 (5034): 954–5. doi:10.1126/science.1719636. PMID 1719636
3. http://www.crcnetbase.com/doi/abs/10.1201/9781420028775.ch3
4. http://www.ccdc.cam.ac.uk/Solutions/GoldSuite/Pages/GOLD.aspx
5. Wei BQ, Weaver LH, Ferrari AM, Matthews BW, Shoichet BK (2004). "Testing a
flexible-receptor docking algorithm in a model binding site". J. Mol. Biol. 337 (5):
1161–82.doi:10.1016/j.jmb.2004.02.015. PMID 15046985
6. http://autodock.scripps.edu/
7. http://www.ibms.kmu.edu.pk/sites/ibms.kmu.edu.pk/files/downloads/Dr.%20Abdu
l%20Wadood.pdf