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Drug Design Presentation

This document discusses molecular docking as a computational technique used in drug discovery to predict how ligands bind to protein targets. It describes the methodology which involves pharmacophore modelling to identify candidate molecules and molecular docking simulations to analyze binding. Results show the selected potent ligand interacting well in the binding pocket. The study helps in early drug discovery but more analysis is needed before potential drug activity.

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Aneez Mohamed
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34 views11 pages

Drug Design Presentation

This document discusses molecular docking as a computational technique used in drug discovery to predict how ligands bind to protein targets. It describes the methodology which involves pharmacophore modelling to identify candidate molecules and molecular docking simulations to analyze binding. Results show the selected potent ligand interacting well in the binding pocket. The study helps in early drug discovery but more analysis is needed before potential drug activity.

Uploaded by

Aneez Mohamed
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PDF, TXT or read online on Scribd
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MOLECULAR DOCKING:

• Molecular docking is a computational technique used in drug discovery to predict


how small molecules (ligands) bind to a target protein's active site

• It aims to predict the binding mode of a compound for a given receptor as well as
the quality of the interaction and strength of noncovalent bond.

• A scoring function is used to estimates the strength of the connection or binding


affinity.

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Disease
• Schizophrenia, a chronic brain disorder in which people interpret reality
abnormally.
• May result in some combination of hallucinations, delusions, and extremely
disordered thinking and behavior that impairs daily functioning, and can be
disabling.
Protein
7DFP: It is the structure of the dopamine D 2 receptor in complex with the
antipsychotic drug spiperone

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METHODOLOGY:
a) PHARMACOPHORE MODELLING
• Identify a disease and select an appropriate target protein from RCSB-PDB
• Search for the Target protein in the Pharmacophore modelling software
‘Pharmit’
• Refine the search as required
• Select a database to start the search for molecules and conformers
• Further analyze and prioritize the results
• Click ‘Save’ to download the list of candidate molecules
• The list of molecules can be viewed in Biovia Discovery Studio.

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b) MOLECULAR DOCKING
➢Search the required protein from protein databank and download
➢Swiss PDB Viewer: Purify the protein is prepared
➢PyRx software: Import the ligand; minimize and convert to pdbqt format
Load the purified protein and convert it to macromolecule
Adjust the grid size
Select all ligands & purified protein; Click forward in vina wizard
On completion save the score in .csv format; scores are obtained
➢PyMol Software: Import the potent ligand & purified protein
Save as drug-complex.pdb format
➢Biovia Discovery Studio: Open the drug-complex.pdb
The 2-D protein ligand interaction is obtained
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RESULTS AND DISCUSSION
In Pharmit, protein is elucidated by:
• The conformational space of the flexible molecules were coeverd extensively
• Molecules were aligned by common pharmacophore features
Molecular Docking
• The ligand with the highest negative Gibb’s free energy and RMSD value 0 was
selected
• The ligand-protein complex gives information of the amino acids responsible for
interactions
• Also other interactions like Van der Waal’s Force, hydrogen bond, Pi-sigma &Pi-Pi
interactions were obtained
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RESULTS AND DISCUSSION
Pharmacophore Modelling:

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Molecular Docking:
CONCLUSION
The potent ligand chosen based on the optimum score, helps to estimate how
well the ligand fits and interacts with the protein's binding pocket.

However, this is a primitive molecular docking study and various other


parameters need to be analysed before their activity against the target protein
is considered to be potential drugs.

Employment of CADD techniques is helpful in the preliminary stage of drug


discovery, it is more cost-efficient and minimize failures in the final stage.

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References
• Muhammed, M. Yalcin, E. (2021) Pharmacophore Modelling in Drug
Discovery:Methodology and Current Status. Journal of the Turkish Chemical
Society. <https://dergipark.org.tr/en/download/article-file/1731809>
• Raval, K. Ganatra, T. (2022) Basics, types and applications of Molecular Docking: A
Review. IP International Journal of Comprehensive and Advanced Pharmacology
<https://www.ijcap.in/html-article/16019#idm139948998430608>
• Qing, X. Lee, X.Y. Raeymaecker, J. Tame, J. Zhang, K. Maeyer, M. Voet, A. (2014)
Pharmacophore Modelling: Advances, Limitations and Current utility in Drug
Discovery. Dovepress. <https://www.dovepress.com/pharmacophore-modeling-
advances-limitations-and-current-utility-in-dru-peer-reviewed-fulltext-article-
JRLCR>

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THANK YOU

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