PROTEIN FOLD RECOGNITION AND DYNAMICS IN THE SPACE OF CONTACT MAPS

We introduce an energy function for contact maps of proteins. In addit ion to the standard term, that takes into account pairwise interaction s between amino acids, our potential contains a new hydrophobic energy term. Parameters of the energy function were obtained from a statisti cal analysis of the contact maps of known structures. The quality of o ur energy function was tested extensively in a variety of ways. In par ticular, fold recognition experiments revealed that for a fixed sequen ce the native map is identified correctly in an overwhelming majority of the cases tested. We succeeded in identifying the structure of some proteins that are known to pose difficulties for such tests (BPTI, sp ectrin, and cro-protein). In addition, many known pairs of homologous structures were correctly identified, even when the two sequences had relatively low sequence homology, We also introduced a dynamic Monte C arlo procedure in the space of contact maps, taking topological and po lymeric constraints into account by restrictive dynamic rules. Various aspects of protein dynamics, including high-temperature melting and r efolding, were simulated. Perspectives of application of the energy fu nction and the method for structure checking and fold prediction are d iscussed. (C) 1996 Wiley-Liss, Inc.