Patent ID: 6178384
Filing Date: 2001-01-23
Classification: G16B,G16C

Abstract:
A method of using a computer processor to analyze electrical signals and data representative of a first molecule to determine conformational free energy of the first molecule so as to determine whether the first molecule is more stable than a second molecule, wherein both molecules have a predefined connectivity and exist in a predefined environment, comprising:(a) generating a set of data representative of low-energy minimum conformations of the first molecule derived from connectivity of the first molecule, a potential energy function, and a conformational search method;(b) determining conformational free energy of the first molecule by calculating a configuration integral in all degrees of freedom based upon a contribution of each conformation of the set of conformations of the first molecule, wherein the configuration integral is calculated by:(i) performing importance sampling multidimensional Monte Carlo integration over a multidimensional volume enclosing a current conformation of the first molecule in a conformational space,wherein the volume is dependent on harmonic vibrational frequencies of the current conformation and temperature,wherein the importance sampling comprises preferentially sampling regions of the volume in conformational space associated with the current conformation which regions have dominant contribution to the conformational free energy of the current conformation, andwherein the importance sampling utilizes a physical background consisting essentially of normal modes of vibration of the first molecule and the sampling is performed using an atomic coordinate transformation which is based on eigenvectors of a Hessian matrix associated with the current conformation;(ii) repeating step (i) for each conformation in the set of data; and(iii) summing the conformational contributions determined in steps (i-ii) so as to determine a total configuration integral for the first molecule to determine the conformational free energy of the first molecule;(c) repeating steps (a)-(b) for the second molecule; and(d) comparing the conformational free energy of the first molecule with the conformational free energy of the second molecule and determining which molecule has lower conformational free energy to determine which molecule is more stable.