Topics and Course Organization
Day One - 21 January
Introduction (9:00-10:30)
Preliminaries and Introductions
Overview of Molecular Structure
The Role of Molecular Structure in Drug Discovery
Basic Principles of Crystallography
Q&A session 1 (15 min)
Coffee Break (10:30 – 10:45)
Protein Crystallization (10:45-12:00)
Fundamentals of Protein Crystallization
Crystallization Techniques (with demonstration)
Crystallization Screening – Design Strategies
Optimization
Evaluation and Statistical Predictions
Cryoprotection
Crystal Harvesting
Lunch (12:00-13:00)
From Data to Structure (13:00-14:45)
From Data to Structure
Data Collection Strategies
Phasing Principles and Examples
Phase Extension
Model Building
Model Refinement
Q&A session 3 (15 min)
Coffee Break (14:45 – 15:00)
From Structure to Knowledge (15:00-16:30)
Validation of Protein Target Structures
Visualization, Analysis and Interpretation of Crystal Structures
Crystallographic Lead Optimization
Crystallographic Fragment Analysis
Q&A session 4 (15 min)
Review and Wrap-up Discussions (16:30 – 17:00)
Day Two - 22 January
Overview: Challenges in Structure-Based Drug Discovery (09:00-9:45)
Drug-Receptor Structure: Molecular Modeling and Structure Analysis (9:45-10:15)
Linking sequence to structure
Homology modeling
Coffee Break (10:15 – 10:30)
Drug-Receptor Structure: Molecular Modeling and Structure Analysis (10:30-11:30)
Loop modeling
Critical model analysis
Model refinement and simulations
Predicting Drug Binding Pockets and Interaction Sites (11:30-12:00)
Identifying ligand binding pockets
Lunch (12:00-13:00)
Predicting Drug Binding Pockets and Interaction Sites (13:00-13:30)
Predicting protein-protein interaction sites
Predicting Drug Receptor Interaction: Ligand Docking (14:00-15:00)
Crystal and model structure preparation for docking – potential pitfalls
Rigid small-molecule docking
Induced fit and flexibility, fully flexible ligand and receptor docking
Template docking
Predicting ligand receptor binding energies Ligand scoring and binder discrimination
Coffee Break (15:00 – 15:15)
Identifying New Drug Leads: Virtual Screening and Cheminformatics (15:15-15:45)
Drug databases and cheminformatics
Virtual screening
QSAR
Modeling and Simulating Biochemical Reactions of Drug Targets: (15:45-16:30)
Requirements of each in silico method with regard to the underlying molecular model Hybrid quantum mechanical/molecular mechanical methods
Molecular dynamics
Nonproductive structures and models
Review and Wrap-up Discussions (16:30 – 17:00)