Prediction of protein-folding mechanisms from free-energy landscapes derived from native structures

摘要: Guided by recent experimental results suggesting that protein-folding rates and mechanisms are determined largely native-state topology, we develop a simple model for protein folding free-energy landscapes based on structures. The configurations considered the contain one or two contiguous stretches of residues ordered as in native structure with all other completely disordered; free energy each configuration is difference between entropic cost ordering residues, which depends total number length loop segments, favorable attractive interactions, taken to be proportional surface area buried structure. Folding kinetics modeled allowing only residue become ordered/disordered at time, rigorous exact method used identify maxima lowest paths connecting fully disordered configurations. distribution these maxima, comprise transition-state ensemble model, reasonably consistent data transition state five seven proteins studied. Thus, appears capture, least part, basic physics underlying aspects topology determine mechanisms.