Conformational search of peptides and proteins: Monte Carlo minimization with an adaptive bias method applied to the heptapeptide deltorphin.

The energy function of a protein consists of a tremendous number of minima. Locating the global energy minimum (GEM) structure, which corresponds approximately to the native structure, is a severe problem in global optimization. Recently we have proposed a conformational search technique based on the Monte Carlo minimization (MCM) method of Li and Scheraga, where trial dihedral angles are not selected at random within the range [-180 degrees,180 degrees ] (as with MCM) but with biased probabilities depending on the increased structure-energy correlations as the GEM is approached during the search. This method, called the Monte Carlo minimization with an adaptive bias (MCMAB), was applied initially to the pentapeptide Leu-enkephalin. Here we study its properties further by applying it to the larger peptide with bulky side chains, deltorphin (H-Tyr-D-Met-Phe-His-Leu-Met-Asp-NH(2)). We find that on average the number of energy minimizations required by MCMAB to locate the GEM for the first time is smaller by a factor of approximately three than the number required by MCM-in accord with results obtained for Leu-enkephalin. Copyright 2004 Wiley Periodicals, Inc. J Comput Chem 25: 565-572, 2004