Molecular Modelling and Docking

Syllabus Overview

 Molecular Modelling & Molecular Docking

4 Weeks Program (16 Classes | 1 Hour per Day)

Level: PG / Advanced

Focus: 30% Theory | 70% Hands-on

Week 1 — Introduction to Molecular Modelling & Structural Preparation

Class 1: Introduction to Molecular Modelling & Drug Discovery

Objective: Understand molecular modelling concepts and applications in drug discovery

✓ What is Molecular Modelling?

✓ Role in Computer-Aided Drug Design (CADD)

✓ Structure-Based vs Ligand-Based Drug Design

✓ Overview of Drug Discovery Pipeline

✓ Applications in pharma, biotechnology & research

Hands-on:

✓ Introduction to PyMOL interface

✓ Load a sample protein structure

✓ Basic structure visualization & representation styles

Class 2: Protein Structure & Databases

Objective: Learn protein structural organization and database retrieval

✓ Levels of protein structure (Primary → Quaternary)

✓ Experimental structure determination (X-ray, NMR, Cryo-EM)

✓ Introduction to Protein Data Bank

✓ Understanding PDB format

Hands-on:

✓ Download protein structure from PDB

✓ Identify chains, ligands, heteroatoms

✓ Remove water molecules

✓ Save cleaned structure

Class 3: Force Fields & Energy Minimization

Objective: Understand molecular mechanics and energy calculations

✓ Molecular mechanics theory

✓ Bonded vs non-bonded interactions

✓ Popular force fields (AMBER, CHARMM)

✓ Concept of energy minimization

Hands-on:

✓ Energy minimization using UCSF Chimera

✓ Structural evaluation

✓ Ramachandran plot analysis

Class 4: Protein Preparation for Docking

Objective: Prepare receptor structure for docking

✓ Protein cleaning workflow

✓ Adding hydrogens & charges

✓ Receptor preparation principles

Hands-on:

✓ Prepare receptor using AutoDock Tools

✓ Convert PDB → PDBQT

✓ Save docking-ready receptor

Week 2 — Ligand Preparation & Binding Site Analysis

Class 1: Ligand Basics & Drug-Likeness

Objective: Understand ligand properties and drug-likeness

✓ Chemical file formats (SMILES, SDF, MOL)

✓ 2D vs 3D structures

✓ Lipinski Rule of Five

✓ ADME basics

Hands-on:

✓ Retrieve ligand from PubChem

✓ Download SDF structure

Class 2: Ligand Preparation Workflow

Objective: Convert and optimize ligand for docking

✓ Protonation & charge assignment

✓ Conformer generation

✓ Ligand flexibility

Hands-on:

✓ Convert SDF → PDB using Open Babel

✓ Add hydrogens

✓ Generate PDBQT ligand file

Class 3: Active Site Prediction

Objective: Identify potential binding pockets

✓ Binding pocket concept

✓ Blind vs targeted docking

✓ Grid box fundamentals

Hands-on:

✓ Active site prediction using CASTp

✓ Visualize binding site

Class 4: Grid Preparation & Docking Setup

Objective: Define docking parameters

✓ Grid box dimensions

✓ Coordinates (X, Y, Z)

✓ Exhaustiveness concept

Hands-on:

✓ Define grid box in AutoDock Tools

✓ Prepare configuration file for docking

Week 3 — Molecular Docking Execution & Analysis

Class 1: Principles of Molecular Docking

Objective: Understand docking algorithms & scoring

✓ Lock & Key Model

✓ Induced Fit Model

✓ Rigid vs Flexible Docking

✓ Scoring functions & binding affinity

Hands-on:

✓ Setup AutoDock Vina environment

Class 2: Running Docking Simulation

Objective: Perform protein-ligand docking

✓ Docking command structure

✓ Understanding output logs

Hands-on:

✓ Run docking using AutoDock Vina

✓ Extract binding affinity values

✓ Compare docking poses

Class 3: Docking Result Visualization

Objective: Analyze docking interactions

✓ RMSD interpretation

✓ Selecting best pose

Hands-on:

✓ Visualize docking results using Discovery Studio Visualizer

✓ Identify hydrogen bonds, hydrophobic & π interactions

Class 4: 2D Interaction Mapping & Comparative Docking

Objective: Generate interaction diagrams & compare ligands

✓ Importance of 2D interaction plots

✓ Comparative docking strategy

Hands-on:

✓ Generate 2D interaction maps

✓ Dock 2–3 ligands

✓ Create docking score comparison table

Week 4 — Validation, Advanced Concepts & Mini Project

Class 1: Docking Validation & Limitations

Objective: Understand reliability of docking results

✓ Re-docking concept

✓ Cross-validation

✓ False positives

✓ Limitations of docking

Hands-on:

✓ Perform re-docking

✓ Compare RMSD values

Class 2: Virtual Screening Basics

Objective: Introduction to screening multiple ligands

✓ Virtual screening workflow

✓ High-throughput docking concept

✓ Ranking ligands

Hands-on:

✓ Dock multiple ligands

✓ Rank based on binding energy

Class 3: Mini Project – Execution

Objective: Apply full workflow independently

Hands-on (Full Session):

✓ Select protein target

✓ Prepare receptor

✓ Prepare 3 ligands

✓ Perform docking

✓ Generate interaction diagrams

Class 4: Project Presentation & Discussion

Objective: Interpret and present results scientifically

✓ Result interpretation

✓ Discussion of biological significance

✓ Troubleshooting common errors

Hands-on:

✓ Student presentation

✓ Viva & feedback