Preparation of 3D-Coordinate from Chemical Structural Formula

Abstract

Obtaining three-dimensional coordinate of chemical substrates from its structural formula is a crucial process in drug design. We here discuss existing methodology and programs, and compare them with a method we developed. Our method is based on a simplified distance geometry algorithm followed by force field optimization. Repetitive generation of structure provides fairly stable conformer in reasonable timescale even for molecules with rather flexible ring systems. Validation of structures was made by flexible fitting with CSD X-ray structure. More than 80% of five thousands converted geometries are found within less than 0.3 angstrom RMSD from the experimental structures.