#1AI-Assisted Virtual Screening for Hypertension Drug Discovery using AutoDock

Module 1 (1 Hour) – Fundamentals of Drug Discovery for Hypertension

Objective: Give participants a strong foundation in hypertension biology and computational drug discovery.

• Topics

  • Hypertension: causes, prevalence, and treatment approaches.

  • Drug discovery pipeline: from target identification to clinical trials.

  • Why computational methods matter: cost, time savings, early-stage filtering.

  • Introduction to AutoDock / AutoDock Vina.

  • Target protein in hypertension: Angiotensin-Converting Enzyme (ACE).

• Activity

  • Explore ACE protein structure on RCSB PDB.

  • Identify active site residues from literature.

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Module 2 (1 Hour) – Setting Up the Environment

Objective: Install and configure AutoDock and required tools.

• Topics

  • Installing AutoDock Vina, AutoDock Tools, PyRx (GUI alternative).

  • Installing OpenBabel for file conversions.

  • File formats: .pdb, .pdbqt, .mol2, .sdf.

• Activity

  • Download ACE enzyme structure (PDB ID: 1O86).

  • Prepare working directories for docking.

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Module 3 (1 Hour) – Preparing Protein & Ligands

Objective: Process protein and ligands for docking.

• Topics

  • Protein preparation:

    • Remove water molecules.

    • Add hydrogens and charges.

    • Save in .pdbqt format.

  • Ligand preparation:

    • Obtain known antihypertensive drugs (e.g., Lisinopril, Enalapril, Captopril) from PubChem.

    • Convert from SMILES to 3D structures.

    • Energy minimization.

    • Save in .pdbqt format.

• Activity

  • Hands-on with AutoDock Tools to prepare protein and one ligand.

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Module 4 (1 Hour) – Running Docking Simulations

Objective: Perform molecular docking with AutoDock Vina.

• Topics

  • Understanding docking parameters:

    • Grid box center and size.

    • Exhaustiveness.

  • Command-line docking with Vina.

  • Using PyRx for GUI docking.

• Activity

  • Run docking for one ligand against ACE.

  • Save and analyze binding affinity results.

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Module 5 (1 Hour) – Analyzing Results & Ranking Compounds

Objective: Interpret docking results and discuss next steps.

• Topics

  • Reading AutoDock Vina output.

  • Understanding binding affinity (kcal/mol).

  • Visualizing poses in PyMOL or PyRx.

  • Ranking multiple ligands.

  • Limitations of docking and need for further validation.

• Activity

• Visualize top binding pose for best ligand.

• Rank 3–5 ligands by docking score.

• Discuss why the top hit may or may not be the best real-world candidate.

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