Application of Protein Modeling to Drug Discovery

Abstract

The decipherment of the human gene has been completed and the analysis of comprehensive structure and mechanism of proteins are currently being performed in the U.S., Europe and Japan. Pharmaceutical companies are utilizing gene and protein information for determining the concept of the new projects and for inventing new compounds. One such an approach is the Structure-Based Drug Design, SBDD. It is drug design process in which the three dimensional structural information of a protein is used directly. Recently, due to the progress in structural analysis, the number of structures being solved is increasing rapidly. Even when the structure of the target-protein is unknown, it is possible to produce a model structure based on the crystal structure of the homologous protein. Many software have been developed for this purpose and some of them can be used on the internet. In this paper, we will introduce the methodology of molecular modeling and docking simulation briefly, and describe some points that should be taken into account when performing simulations. In addition, we will describe the application to drug design using an acetylcholinesterase, AChE, inhibitor as an example. This paper is based on the lecture presented at the BMS conference in last year.