Molecular docking.pptx

molecular docking.
componenets of molecular docking.
application of molecular docking.
how docking works.

1. Molecular docking Presented by Diptanshu Sawai( b.pharm final year) Dadasaheb balpande college of pharmacy, Nagpur​

2. Introduction 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. 3 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. 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. 4 MOLECULAR DOCKING

5. 5 MOLECULAR DOCKING This Photo by Unknown Author is licensed under CC BY COMPONENTS OF MOLECULAR DOCKING PROTEINS LIGAND DOCKING GRID BOX

6. Types of Molecular Docking Rigid docking Flexible docking 6 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.  Rigid docking is most commonly used for protein to protein docking. It reflects the “lock and key” model of binding. 7 MOLECULAR DOCKING

8. FLEXIBLE DOCKING Flexible docking is a type of molecular docking that models changes in 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. 8 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 9 MOLECULAR DOCKING

10. Workflow of Molecular Docking 10 MOLECULAR DOCKING

11. 11 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. 12 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. 13 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. 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. 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. Molegro Virtual Docker (MVD): Developed by Molegro ApS . Offers user-friendly graphical interfaces. Suitable for ligand-protein and protein-protein docking. Surflex -Dock: Developed by Tripos. Focuses on ligand conformational sampling and scoring. Used for lead optimization and virtual screening. 14 presentation title

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. 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. Molegro Virtual Docker (MVD): Developed by Molegro ApS . Offers user-friendly graphical interfaces. Suitable for ligand-protein and protein-protein docking. Surflex -Dock: Developed by Tripos. Focuses on ligand conformational sampling and scoring. Used for lead optimization and virtual screening. 15 presentation title

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. 16 presentation title

17. APPLICATION OF MOLECULAR docking 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. 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. 17 presentation title

18. APPLICATION OF MOLECULAR docking 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. 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. 18 presentation title

19. APPLICATION OF MOLECULAR docking 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. 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. 19 presentation title

20. APPLICATION OF MOLECULAR docking 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. Repurposing Existing Drugs: Docking is used to identify new therapeutic uses for existing drugs, a process known as drug repurposing. 20 presentation title

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. versatility and predictive capabilities make it a cornerstone of modern scientific exploration and drug development. 21 presentation title

22. Thank you Diptanshu Sawai [email protected]