📅 Day 1: Target Discovery, Validation and Compound Shortlisting
Focus: Identifying a disease-relevant therapeutic target and building a focused compound library for downstream computational screening.
Topics Covered
- Introduction to AI-assisted target discovery and early-stage drug discovery workflows.
- Disease-gene association and therapeutic target identification.
- Biological relevance, druggability and target-prioritisation criteria.
- Protein-function annotation and pathway-level interpretation.
- Protein-protein interaction network analysis.
- Exploration of chemical and bioactivity databases.
- Retrieval of known ligands, inhibitors and related bioactive compounds.
- Molecular descriptors and physicochemical property analysis.
- Drug-likeness and lead-likeness based compound filtering.
- Development of a focused compound library for virtual screening.
🛠️ Hands-on Activities
- Identify disease-associated genes using public biomedical databases.
- Prioritise a therapeutic protein target based on biological and network evidence.
- Analyse the selected target's protein interaction network.
- Retrieve relevant bioactive compounds from PubChem and ChEMBL.
- Generate molecular descriptors using RDKit.
- Apply basic physicochemical and drug-likeness filters.
- Build a focused compound shortlist for molecular docking.
🧰 Tools Covered:
GeneCards, UniProt, STRING, PubChem, ChEMBL, RDKit, Python, Google Colab.
📅 Day 2: Virtual Screening, Molecular Docking and Interaction Analysis
Focus: Evaluating shortlisted compounds against the selected protein target using structure-based computational screening and protein-ligand interaction analysis.
Topics Covered
- Principles of structure-based virtual screening and molecular docking.
- Retrieval and evaluation of experimentally determined protein structures.
- Protein cleaning, hydrogen addition and structural preparation.
- Ligand preparation, protonation and geometry optimisation.
- Identification of active sites and ligand-binding pockets.
- Selection of docking-grid coordinates and search-space parameters.
- Configuration of docking exhaustiveness and pose-generation settings.
- Interpretation of docking scores, binding affinities and pose orientations.
- Analysis of hydrogen bonds, hydrophobic interactions, salt bridges and aromatic interactions.
- Comparison of candidate binding modes and interaction profiles.
- Limitations of docking scores and importance of biological interpretation.
🛠️ Hands-on Activities
- Retrieve and prepare the selected protein structure.
- Prepare the shortlisted compounds for docking.
- Identify the binding pocket and define the docking search space.
- Perform molecular docking using AutoDock Vina.
- Compare binding scores and top-ranked poses.
- Visualise protein-ligand interactions.
- Generate an interaction-based ranking of the strongest candidates.
🧰 Tools Covered:
RCSB Protein Data Bank, PubChem, AutoDock Vina, PyRx, PyMOL, Protein-Ligand Interaction Profiler, Google Colab.
📅 Day 3: AI-Based Activity Prediction, ADMET Profiling and Lead Prioritisation
Focus: Integrating machine-learning predictions, molecular features, docking results and ADMET properties to identify the most promising lead candidates.
Topics Covered
- Molecular fingerprints and descriptor-based compound representation.
- Introduction to QSAR and machine-learning-based activity prediction.
- Preparation of molecular datasets for predictive modelling.
- Random Forest and XGBoost algorithms for compound activity prediction.
- Model training, validation and performance evaluation.
- Interpretation of molecular features using SHAP.
- Prediction of drug-likeness and pharmacokinetic properties.
- Assessment of absorption, distribution, metabolism and excretion.
- Toxicity prediction and medicinal chemistry alerts.
- Integration of docking, predicted activity and ADMET results.
- Multi-parameter lead scoring and compound prioritisation.
- Selection of primary and backup lead candidates.
🛠️ Hands-on Activities
- Generate molecular fingerprints and descriptors using RDKit.
- Build and evaluate a machine-learning activity-prediction model.
- Predict biological activity for shortlisted compounds.
- Interpret important molecular features using SHAP.
- Evaluate drug-likeness and ADMET properties using SwissADME.
- Compare docking, predicted activity and pharmacokinetic results.
- Develop an integrated lead-prioritisation matrix.
- Select the final lead and backup candidates.
🧰 Tools Covered:
Python, RDKit, scikit-learn, XGBoost, SHAP, SwissADME, PubChem, Google Colab, Microsoft Excel or Google Sheets.