Organization and dynamics in the folding of globular proteins

What we have found is that any polymer chain which is caused to be compact by any driving force, will develop internal organization just because of the nature of the severe steric constraints in the compact polymeric state. We find that this distribution of helices and parallel and antiparallel sheets is nearly identical to that observed in the known crystal structures of globular proteins. Our approach has been to use exhaustive computer simulations of all possible configurations of compact polymer chains on simple cubic lattices in 3D and square lattices in 2D. We consider HP chains (H: hydrophobic, P: polar) of all possible monomer sequences. Using the same HP model of chains with a known unique native structure, we have explored the kinetics of folding from the random conformations to the native state. Even though the chains are permitted the freedom to explore all possible conformations, we find that, taken over the full ensemble, some pathways are strongly preferred relative to others. This is consistent with experimental evidence that shows that proteins fold through specific sequences of events.