The Folding Energy Landscape and Free Energy Excitations of Cytochrome c

摘要

Tnhe covalently bound heme cofactor plays a dominant role innthe folding of cytochrome c. Because of the complicated inor-nganic chemistry of the heme, some might consider the foldingnof cytochrome c to be a special case, following principles dif-nferent from those used to describe the folding of proteins with-nout cofactors. Recent investigations, however, demonstrate thatncommon models describing folding for many proteins work wellnfor cytochrome c when heme is explicitly introduced, generallynproviding results that agree with experimental observations.nIn this Account, we first discuss results from simple nativenstructure-based models. These models include attractive inter-nactions between nonadjacent residues only if they are present in the crystal structure at pH 7. Because attractive nonna-ntive contacts are not included in native structure-based models, their energy landscapes can be described as “perfectlynfunneled”. In other words, native structure-based models are energetically guided towards the native state and contain nonenergetic traps that would hinder folding. Energetic traps are denoted sources of “frustration”, which cause specific tran-nsient intermediates to be populated.