Program Structure

Module 1: Structure-Based Drug Design — The Core Idea

• Why structure matters: binding site, interactions, and selectivity.
• Hit vs lead vs optimized candidate: how SBDD supports each stage.
• Strengths and limitations of in silico screening (what to trust and what not to).
• Choosing a target: druggability, relevance, and available structural evidence.

Module 2: Protein Structures & Binding Site Identification

• Finding structures: PDB basics, resolution, ligands, chains, and biological assemblies.
• Binding site identification: co-crystal ligands, known residues, pocket detection (concept).
• Understanding cofactors, metals, water networks, and why they matter.
• Assessing structure quality: missing residues, mutations, alternate conformations.

Module 3: Protein Preparation (Make the Target Docking-Ready)

• Cleaning and fixing structures: missing atoms/residues (concept), protonation, charges.
• Deciding about waters: when to keep/remove them and why.
• Adding hydrogens and selecting correct states (pH considerations overview).
• Defining the docking box/grid correctly for meaningful results.

Module 4: Ligand Preparation & Library Building

• SMILES to 3D: conformers, minimization, stereochemistry basics.
• Tautomers and ionization states: how they change docking outcomes.
• Building a small screening library: sources, curation, and duplicates.
• Property checks: basic drug-likeness and “avoid obvious bad actors.”

Module 5: Molecular Docking (Hands-on Screening Workflow)

• Docking fundamentals: scoring, search, poses, and ranking logic.
• Single-ligand docking vs batch docking: when and why.
• Reading results: docking score + interaction quality + pose plausibility.
• Interaction analysis: H-bonds, hydrophobic contacts, salt bridges, π interactions.

Module 6: Validation & Quality Control (Don’t Trust the Wrong Pose)

• Redocking and RMSD: checking whether your docking setup is reliable.
• Positive/negative controls: how to set expectations for your workflow.
• Common pitfalls: overfitting the grid, unrealistic protonation, wrong pocket.
• Rescoring and consensus thinking (overview) for better confidence.

Module 7: Hit Prioritization & Lead Optimization Thinking

• From hit list to shortlist: practical ranking criteria beyond score.
• Interaction-driven optimization: what to modify and why.
• Basic ADMET and safety flags (concept): solubility, permeability, toxicity risks.
• Designing “next round” compounds: analog selection and rational changes.

Module 8: Beyond Docking (SBDD Extensions — Overview)

• Molecular dynamics (MD) concept: why flexibility matters.
• Binding free energy concepts (MM/PBSA overview).
• Pharmacophore screening and fragment-based ideas (overview).
• How real pipelines combine methods for stronger confidence.

Final Project

• Select a target protein (provided list or your own) and run a structure-based screening workflow.
• Deliverables: prepared protein + ligand set, docking results, interaction analysis, top shortlist, and rationale.
• Include validation notes: redocking/controls and limitations.
• Example projects: enzyme inhibitor screening, receptor ligand shortlist, antimicrobial target screening, cancer target docking study.