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Computer simulation of the folding–unfolding transition of island‐model proteins—folding pathway, transition process, and fluctuations
Author(s) -
Segawa ShinIchi,
Kawai Toshikazu
Publication year - 1986
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360251002
Subject(s) - chemistry , folding (dsp implementation) , downhill folding , protein folding , transition state , reaction coordinate , phi value analysis , folding funnel , thermodynamics , chemical physics , crystallography , computational chemistry , physics , biochemistry , electrical engineering , engineering , catalysis
Monte Carlo computer simulations were performed to elucidate the dynamic aspects of the folding and unfolding transitions of island‐model protein. Five different types of model proteins were designed, according to characteristics of backbone structure. The computer simulations clearly show that the unfolding and folding transitions are all‐or‐none processes between the N‐and U‐states. They are typical Poisson processes. From the Arrhenius plots of rate constants, the activation enthalpies of folding and unfolding were determined. In addition, the folding pathways were determined along the reaction coordinate. Formations of several local structures along a polypeptide chain are almost simultaneous, but the most probable time sequence of events exists at the moment of transition. That is the most probable folding pathway. The unfolding pathway was found to be just the reverse process of the most probable folding pathway. The relationship between the fluctuations in each equilibrium state and the transition process was considered. In contrast to the theory of absolute reaction rate, the transient states are widely distributed along the reaction coordinate. From analysis of the “transient process,” we tried to determine the critical states from which the transient process starts. As a result, we found that the unfolding transition occurs at the stage near the N‐state. During the U‐state, large joined blocks rarely appear, but they appear in the transient process towards the N‐state. However, the “branch point” between the N‐ and U‐states lies near the N‐state, and joined blocks tend to unfold prior to passing over the branch point. We concluded that the stability of later folding intermediates is important for selection of the folding pathway, while preferential selection of an early folding intermediate is important in acceleration of the folding rate. The effects of intrachain cross‐linking and peptide fragment binding on the rate constants were examined by using computer simulations of model proteins. In general, a small‐sized loop formed by cross‐linking accelerates the folding rate and a large‐sized loop contributes much to the stabilization of the native conformation. We also found that peptide fragment binding contributes little to the acceleration of the folding rate of the residual protein.