On the multiple-minima problem in the conformational analysis of polypeptides. IV. Application of the electrostatically driven Monte Carlo method to the 20-residue membrane-bound portion of melittin

The conformational space of the membrane-bound portion of melittin has been searched using the electrostatically driven Monte Carlo (EDMC) method with the ECEPP/2 (empirical conformational energy program for peptides) algorithm. The former methodology assumes that a polypeptide or protein molecule is driven toward the native structure by the combined action of electrostatic interactions and stochastic conformational changes associated with thermal movements. The algorithm produces a Monte Carlo search in the conformational hyperspace of the polypeptide using electrostatic predictions and a random sampling technique, combined with local minimization of the energy function, to locate low-energy conformations. As a result of 8 test calculations on the 20-residue membrane-bound portion of melittin, starting from six arbitrary and two completely random conformations, the method was able to locate a very low-energy region of the potential with a well-defined structure for the backbone. In all of the cases under study, the method found a cluster of similar low-energy conformations that agree well with the structure deduced from x-ray diffraction experiments and with one computed earlier by the build-up procedure.