一、課程簡介:

Computational Drug Discovery and Design

Successful Examples using Computational Approaches for Drug Design
HIV-protease
Cytochrome P450
G-protein coupled receptors
FKBP

Molecular Interactions
Coulomb Interactions
Van der Waals Interactions
Hydrogen Bonds
Covalent Bonds
Electrostatics in solution
Hydrodynamic Interactions

Modeling Biological Macromolecules
Force Field Formalism
Water
Ions
Amino Acids, Peptides, and Proteins
Nucleic Acids, RNA, and DNA
Lipids
Polarizable Force Fields
Quantum Mechanics/Molecular Mechanics (QM/MM) Approaches

Sampling Phase Spaces of Biomolecules
Monte Carlo Methods
Importance Sampling
Markovian Chain and the Master Equation
Metropolis Algorithm
Molecular Dynamics Methods
Newtonian Equation of Motion
Extension from NVE to NPT ensemble
Limitation of the Time Scale
Hybrid Methods

Docking as a Global Optimization Problem
Designing the Score Function
Binding Affinity
Free Energy Evaluation
Simulated Annealing
Genetic Algorithm
Original Formalism
Lamarckian Genetic Algorithm
Neural Network
Receptor Flexibility and the Relaxed Complex Scheme
SAR by NMR
the tether method

Pharmacophore Mapping
Three Dimensional Quantitative Structure-Activity Relationships (3D-QSAR)
Identification of Pharmacophores
Dynamic Pharmacophore Methods

Toward Virtual Screening of Compounds
Evaluating Structures obtained from Experimental Approaches
Protein Structure Prediction
Protein Folding Kinetics
Drug Library Design and Use of FDA Databases
Lead Finding and Optimization
Rapid Permeability Screening and Predictive ADME
Computational Toxicology

Computational Genomics and Proteomics
Identification and Prediction of Genes
Use of SNP Pharmacogenetics for Drug Design


二、先修課程:

Physical Chemistry, General Physics

三、參考書目:

Leach, Andrew R. (2001). Molecular Modelling. Principles and Applications. Longman Publisher Ltd.