Exploring conformational space using a mean field technique with MOLS sampling

The computational identification of all the low energy structures of a peptide given only its sequence is not an easy task even for small peptides, due to the multiple-minima problem and combinatorial explosion. We have developed an algorithm, called the MOLS technique, that addresses this problem, and have applied it to a number of different aspects of the study of peptide and protein structure. Conformational studies of oligopeptides, including loop sequences in proteins have been carried out using this technique. In general the calculations identified all the folds determined by previous studies, and in addition picked up other energetically favorable structures. The method was also used to map the energy surface of the peptides. In another application, we have combined the MOLS technique, using it to generate a library of low energy structures of an oligopeptide, with a genetic algorithm to predict protein structures. The method has also been applied to explore the conformational space of loops in protein structures. Further, it has been applied to the problem of docking a ligand in its receptor site, with encouraging results.