Protein folding bottlenecks: A lattice Monte Carlo simulation

Abstract
Results of Monte Carlo simulations of folding of a model ‘‘protein,’’ which is a freely joined 27-monomer chain on a simple cubic lattice with nearest-neighbor interactions, are reported. All compact self-avoiding conformations on this chain have been enumerated, and the conformation (‘‘native’’) corresponding to the global minimum of energy is known for each sequence. Only one out of thirty sequences folds and finds the global minimum. For this sequence, the folding process has a two-stage character, with a rapid noncooperative compactization followed by a slower transition over a free-energy barrier to the global minimum. The evolutionary implications of the results are discussed.