  Here we study the effects of many-body interactions on rate and mechanism in
protein folding, using the results of molecular dynamics simulations on
numerous coarse-grained C-alpha-model single-domain proteins. After adding
three-body interactions explicitly as a perturbation to a Go-like Hamiltonian
with native pair-wise interactions only, we have found 1) a significantly
increased correlation with experimental phi-values and folding rates, 2) a
stronger correlation of folding rate with contact order, matching the
experimental range in rates when the fraction of three-body energy in the
native state is ~ 20%, and 3) a considerably larger amount of 3-body energy
present in Chymotripsin inhibitor than other proteins studied.
