Protein folding in contact map space

Changing a few contacts in a contact map corresponds to a large scale move in confrontation space; hence, one gains a lot by using the contact map rep resentation for protein folding. We developed an efficient search procedure in the space of physical contact maps, which could identify the native fol d as of the lowest free energy, provided on had a free energy function whos e ground state is the native map. We prove rigorously that the widely used pairwise contact approximation to the free energy cannot stabilize even a s ingle protein's native map. Testing the native map against a set of decoys obtained by gapless threading, one may be misled to the opposite conclusion . [S0031-9007(98)08231-3].