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 representation for protein folding. We developed an efficient search procedure in the space of physical contact maps, which could identify the native fold as of the lowest free energy, provided on had a free energy function whose ground state is the native map. We prove rigorously that the widely used pairwise contact approximation to the free energy cannot stabilize even a single 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].