[Rinsho Byori 50 : 45-51, 2002]

An Introduction to the Computer-Aided Structure-Based Drug Design
--Applications of Bioinformatics to Drug Discovery--

Shuichi HIRONO, PhD*

Computer-aided drug design methods are effective tools for drug discoveries.
It is only small number of compounds that are required to be synthesized in practice, if the computer-aided drug design methods are used to predict the activities of the compounds. The methods are based on the interaction theory between drugs and their target proteins. Steric, electrostatic and hydrophobic complementarities are important in the interaction between the drug and the target protein. When three-dimensional structures of target proteins are known, the method is called as a structure-based drug design, while in case that the structures are unknown, a ligand-based drug design approach is employed for the computer-aided rational drug design. In the computer-aided structure-based drug design, it is important to build up the three-dimensional structure of drug-protein complex and to calculate a binding affinity of the drug to the protein. A molecular dynamics/free energy calculation is one of the most powerful tools to predict the binding affinity of a ligand molecule, when the three-dimensional structure of the drug-protein complex is available. The molecular dynamics/free energy calculation has been able to evaluate the binding affinities of a lot of ligand molecules to the target proteins successfully.

*School of Pharmaceutical Sciences, Kitasato University, Minato-ku, Tokyo 108-8641