TORSIONAL FLEXING - CONFORMATIONAL SEARCHING OF CYCLIC MOLECULES IN BIASED INTERNAL COORDINATE SPACE

A new stochastic (Monte Carlo) procedure, termed torsional flexing, has been devised for searching the conformational space of cyclic molecules. Torsional flexing causes a local, torsion angle-biased, distortion of a ring bond in a cyclic molecule. Because torsional flexing does not cause large atomic movements, even when it is applied to several bonds simultaneously, subsequent energy minimization generally proceeds rapidly. Nevertheless, the torsional flexing method is prone to generate structures that cross energy barriers so that the structure resulting after energy minimization is frequently a different conformer of the cyclic molecule. Conformational searches on cycloheptadecane, oxobrefeldin A, cyclopenta-L-alanine, and rifamycin SV based upon torsional flexing indicated that torsional flexing is among the best methods yet devised for searching the conformational space of flexible cyclic molecules.