A FREE-ENERGY BASED MONTE-CARLO MINIMIZATION PROCEDURE FOR BIOMOLECULES

The Monte Carlo minimization (MCM) method of Li and Scheraga (Proc. Na tl. Acad. Sci. U.S.A. 1987, 84, 6611) is a highly efficient procedure for generating low-energy structures of macromolecules and therefore h as been used extensively. We propose to enhance this method by carryin g out the conformational search with respect to the harmonic free ener gy rather than the energy. This free energy based MCM (FMCM) procedure has been applied initially to the pentapeptide met-enkephalin, modele d by the potential. energy function ECEPP. The results demonstrate tha t FMCM is effective with a negligible extra computational cost and the refore has the potential to become an important computational tool. Th us, within a range of 1 kcal/mol above the global harmonic free energy minimum, structures were generated with energy of up to 8.3 kcal/mol above the global energy minimum(GEM). Also, three conformations were i dentified with lower free energy than that of the GEM structure. Some of these structures are very unlikely to be detected by the usual MCM method.