A method for selecting a molecule based on conformational free energy of one molecule for another molecule

摘要

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, includes 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. Conformational free energy of the first molecule is determined 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, and the configuration integral is calculated by performing importance sampling multidimensional Monte Carlo integration over a multidimensional volume enclosing a current conformation of the first molecule in a conformational space, repeating the integration for each conformation in the set of data, and summing the conformational contributions so as to determine a total configuration integral for the first molecule and thereby determine the conformational free energy of the first molecule.