Speeding protein folding beyond the G(o) model: how a little frustration sometimes helps.

By perturbing a G(o) model toward a realistic protein Hamiltonian by adding non-native interactions, we find that the folding rate is in general enhanced as ruggedness is initially increased, as long as the protein is sufficiently large and flexible. Eventually, the rate drops rapidly toward zero when ruggedness significantly slows conformational transitions. Energy landscape arguments for thermodynamics and kinetics are coupled with a treatment of non-native collapse to elucidate this effect. Copyright 2001 Wiley-Liss, Inc.