Multicanonical procedure for continuum peptide models

The multicanonical (Muca) Monte Carlo method enables simulating a system ov er a wide range of temperatures and thus has become an efficient tool for s tudying spin glasses, first-order phase transitions, the helix-coil transit ion of polypeptides, and protein folding. However, implementation of the me thod requires calculating the multicanonical weights by an iterative proced ure that is not straightforward and is a stumbling block for newcomers. A r ecursive procedure that takes into account the statistical errors of all pr evious iterations and thus enables an automatic calculation of the weights without the need for human intervention after each iteration has been propo sed. This procedure, which has already been tested successfully for lattice systems, is extended here to continuum models of peptides and proteins. Th e method is examined in detail and tested for models of the pentapeptide Le u-enkephalin (Tyr-Gly-Gly-Phe-Leu) described by the potential energy functi on ECEPP. Because of the great interest in the structural mapping of the lo w-energy region of biomolecules, the energy of structures selected from the Muca trajectory is minimized. The extent of conformational coverage provid ed by the method is examined and found to be very satisfactory. (C) 2000 Jo hn Wiley & Sons, Inc.