ANALYSIS OF CONFORMATIONAL COVERAGE .1. VALIDATION AND ESTIMATION OF COVERAGE

Given a topology of a molecule, there are many ways to estimate the si ze and scope of the conformational space.(1-4) This paper studies how well a collection of conformations covers conformational space. A modi fied version of a systematic search was developed to exhaustively sear ch the conformational spaces of small molecules, and a heuristic was a pplied to extract a small set of conformations that covers the space o f the exhaustive set. It demonstrates in principle that a small number of conformations is sufficient to represent the low-energy conformati onal spaces of small to medium-sized molecules. These representative c onformations are used to show that a common empirical measure of flexi bility, the so-called 3(N) estimator, is ineffective at estimating the number of conformations required to cover low-energy conformational s paces.