Molecular docking is a computational technique used in drug discovery to predict how small molecules, like potential drug candidates, bind to protein targets. It involves exploring different orientations of a ligand when bound to the target protein's binding site to form a stable complex. The results of molecular docking help researchers identify ligands that strongly and specifically interact with proteins, guiding drug development and optimization efforts. Key components of molecular docking include the 3D structures of the target protein and ligand, as well as a grid that defines the protein's binding site for efficient sampling of ligand poses. Popular molecular docking software includes AutoDock, DOCK, Glide, and SwissDock.

1. MOLECULAR DOCKING
PRESENTED BY
DIPTANSHU SAWAI(B.PHARM FINAL YEAR)
DADASAHEB BALPANDE COLLEGE OF PHARMACY, NAGPUR​

2. WHAT IS
MOLECULAR
DOCKING?
MOLECULAR
DOCKING
2
•Molecular docking is a computational technique used in
structural biology and drug discovery.
•It involves predicting the preferred orientation of a
ligand (small molecule) when bound to a target protein to
form a stable complex.
•This technique is crucial in drug discovery as it helps
researchers identify potential drug candidates that can
interact with specific protein targets.

3. PROTEIN-LIGAND
INTERACTION
• Protein-ligand interactions are fundamental in biology
and biochemistry.
• Ligands can be small molecules, drugs, or
substrates, and they interact with proteins to trigger
various cellular responses.
• The strength and specificity of these interactions play
a crucial role in biological processes.
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MOLECULAR
DOCKING

4. COMPONENTS OF
MOLECULAR DOCKING
• Protein Structure: The 3D structure of the target protein is a crucial
component. It's typically obtained from experimental techniques like X-ray
crystallography or NMR spectroscopy.
• Ligand Structure: The structure of the ligand, which can be a small
molecule or a drug candidate, is also necessary. It's essential to know the
3D coordinates of the ligand atoms.It can be obtained from DrugBank or
can be drawn with the help of ChemSketch or ChemDraw.
• Grid or Scoring Grid: A grid is often created around the protein's binding
site. It helps in efficiently exploring possible binding orientations and
evaluating interactions within a defined space.
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MOLECULAR
DOCKING

5. 5
MOLECULAR
DOCKING COMPONENTS OF
MOLECULAR DOCKING
PROTEINS LIGAND DOCKING GRID BOX

6. TYPES OF MOLECULAR
DOCKING
1.Rigid docking
2.Flexible docking
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MOLECULAR
DOCKING

7. RIGID DOCKING
• Rigid docking is a molecular docking model that treats the
ligand and target as rigid objects.
• In this model, the molecules cannot change their spatial
shape during the docking process.
• It reflects the “lock and key” model of binding.
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MOLECULAR
DOCKING

8. FLEXIBLE DOCKING
• Flexible docking is a type of molecular docking that
models changes the internal geometry of interacting
partners when a complex is formed.
• Flexible docking allows conformational changes in the
ligand, protein, or both during the docking process.
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MOLECULAR
DOCKING

9. TYPES OF INTERACTION
INVOLVED IN MOLECULAR
DOCKING
•Van der Waals Forces
•Electrostatic Interactions
•Hydrogen Bonds
•Salt Bridges
•π-π Stacking Interactions
•Metal Coordination
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MOLECULAR
DOCKING

10. WORKFLOW OF MOLECULAR
DOCKING
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MOLECULAR
DOCKING
1. 1.Preparation of
the protein and
ligand structures.
2.The Grid
generation to define
possible binding
sites.
3.Ligand pose
generation by
exploring different
orientations and
conformations.
5.Scoring and
ranking of the
generated poses.
4.Analysis and
visualization of the
results.

11. 1 1
MOLECULAR
DOCKING A TYPICAL WORKFLOW OF
DOCKING

12. RECEPTOR, LIGAND
SELECTION AND
PREPARATION
Building the Receptor
The 3D structure of receptor should be considered which can
be downloaded from PDB
The available structure should be processed.
The receptor should be biologically active and stable.
Identification of Active Site
The active site within receptor(protein) should be identified.
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MOLECULAR
DOCKING

13. Ligand selection and preparation
Ligands can be obtained from various database like
PubChem or can be sketched using tools like ChemSketch.
Docking
The ligand is docked onto the receptor and interactions are
checked
The scoring function generates score, depending on which
the best ligand is selected.
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MOLECULAR
DOCKING

14. SOFTWARE'S FOR
DOCKING
 AutoDock/AutoDock Vina:
 Developed by the Scripps Research Institute.
 Widely used for flexible ligand and rigid protein docking.
 Open-source and user-friendly.
 DOCK:
 Developed by the Kuntz group at the University of
California, San Francisco.
 Used for ligand-protein and protein-protein docking.
 Highly customizable but may require scripting skills.
 MGLTools:
 Complements AutoDock and AutoDock Vina.
 Provides a user-friendly interface for preparing input files
and analyzing results.
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15. SOFTWARE'S FOR
DOCKING
 Glide:
 Developed by Schrödinger, Inc.
 Used for high-throughput virtual screening.
 Offers accurate ligand-receptor docking.
 SwissDock:
 Developed by the Swiss Institute of Bioinformatics.
 Web-based and user-friendly.
 Suitable for ligand-protein and protein-protein docking.
 FlexX:
 Developed by BioSolveIT.
 Suitable for flexible ligand and protein docking.
 Used in structure-based drug design.
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16. SOFTWARE'S FOR
DOCKING
 GOLD (Genetic Optimization for Ligand Docking):
 Developed by the University of Cambridge.
 Employs a genetic algorithm for docking.
 Suitable for protein-ligand docking and virtual screening.
 AutoDockFR:
 An improved version of AutoDock.
 Allows flexible receptor and flexible ligand docking.
 Provides a better description of solvation effects.
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17. APPLICATION OF
MOLECULAR DOCKING
1. Drug Discovery and Design:
• One of the most prominent applications of molecular
docking is in drug discovery. It is used to screen and design
potential drug candidates by predicting how well a small
molecule (ligand) binds to a target protein, often an enzyme
or receptor associated with a disease.
2. Protein-Ligand Interaction Studies:
• Molecular docking helps researchers understand the
binding modes and interactions between proteins and
ligands. This insight is crucial for studying molecular
recognition processes, such as substrate binding to
enzymes.
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18. APPLICATION OF
MOLECULAR DOCKING
3. Virtual Screening:
• Virtual screening involves testing large compound libraries
against a specific protein target to identify potential drug
candidates. Molecular docking is a key component of this
process, enabling the rapid evaluation of thousands to
millions of compounds.
4. Lead Optimization:
• After identifying a lead compound, molecular docking
assists in the optimization of its chemical structure to
enhance binding affinity, selectivity, and other
pharmacological properties. This iterative process is vital in
drug development.
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19. APPLICATION OF
MOLECULAR DOCKING
5. Structure-Based Drug Design:
• Molecular docking guides the design of new compounds
with improved binding properties. It enables the exploration
of chemical modifications to create more effective drugs.
6. Protein-Protein Interaction Analysis:
• Molecular docking is used to study protein-protein
interactions, helping researchers understand the
mechanisms underlying various cellular processes, signal
transduction, and disease pathways.
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20. APPLICATION OF
MOLECULAR DOCKING
7. Enzyme Mechanism Elucidation:
• Docking can shed light on the mechanism of enzyme-
catalyzed reactions by simulating the binding of substrates
and products to the enzyme's active site.
8. Repurposing Existing Drugs:
• Docking is used to identify new therapeutic uses for existing
drugs, a process known as drug repurposing.
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21. CONCLUSION
• Molecular docking is predictive power which is invaluable for
accelerating the drug development process, aiding in the
identification of promising drug candidates, and guiding the
design of new drugs.
• Molecular docking also provides a deeper understanding of
protein-ligand and protein-protein interactions, revealing
essential insights into biological mechanisms.
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22. THANK YOU
DIPTANSHU SAWAI
diptanshusawai@gmail.com