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A free energy based Monte Carlo minimization procedure for biomolecules

Journal Article · · Journal of Physical Chemistry; (United States)
DOI:https://doi.org/10.1021/j100089a003· OSTI ID:6904269
 [1]; ;  [2]
  1. Protein Design Lab., Inc., Mountain View, CA (United States)
  2. Florida State Univ., Tallahassee, FL (United States)
The Monte Carlo minimization (MCM) method of Li and Scheraga (Proc. Natl. Acad. Sci. U.S.A. 1987, 84, 6611) is a highly efficient procedure for generating low-energy structures of macromolecules and therefore has been used extensively. We propose to enhance this method by carrying out the conformational search with respect to the harmonic free energy rather than the energy. This free energy based MCM (FMCM) procedure has been applied initially to the pentapeptide met-enkephalin, modeled by the potential energy function ECEPP. The results demonstrate that FMCM is effective with a negligible extra computational cost and therefore has the potential to become an important computational tool. Thus, 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 identified 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. 27 refs., 1 tab.
OSTI ID:
6904269
Journal Information:
Journal of Physical Chemistry; (United States), Journal Name: Journal of Physical Chemistry; (United States) Vol. 98:38; ISSN JPCHAX; ISSN 0022-3654
Country of Publication:
United States
Language:
English