CHEMISTRY 422

Conformations of Molecules and Introduction to
Computer-Aided Drug Design

This course covers modern computational techniques currently used in the conformational analysis of organic and biological molecules and includes an introduction to computer-aided drug design. Lecture course is accompanied by a computer lab where students will obtain practical experience in applying these techniques.

CHEM 213, MATH 111,112, and one of PHYS 105 or 111. (CHEM 224 and MATH 211 Recommended)

The course will be based on the required text (Saferstein). Many case studies will be used to illustrate each topic, and the course will make use of reprint materials.

Introduction:

• Molecular geometry
• Internal and Cartesian coordinates
• Bond length
• Bond angle
• Torsion angle

• Ethane, butane, ethylene, butene, cyclohexane.

Force fields:

• Stretching and bending energy;
• Harmonic approximation. Anharmonicity;
• Torsion energy;
• Rotation around single and double bond;
• Van-der-Waals interactions;
• Exp-6 and Lennard-Jones potentials;
• Parametrization;

• Potential energy surface;
• Stationary points: minima, maxima, saddle points;
• Minimization procedures;

• ECEPP, MM2/MM3, AMBER, CHARMm;

• Multiple minima problem;
• Global minimum;
• Relative importance of conformations;
• Experimental sources of the molecular conformation data;

• Introduction to techniques;

Proteins:

• Primary, secondary, tertiary, and quaternary structures;
• Protein conformations;
• Protein data base (PDB);

Introduction to computer-aided drug design:

• Basics of the molecular mechanism of drug action;
• Guest-host interactions;
• Specific and nonspecific interactions;
• Hydrophobic interactions;
• Docking. Rigid-molecules approximation;
• Conformational change upon complexation;