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Kinetic analysis of local structure formations in protein folding
Author(s) -
Kanehisa Minoru I.,
Tsong Tian Yow
Publication year - 1979
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.1979.360181202
Subject(s) - chemistry , cluster (spacecraft) , population , crystallography , folding (dsp implementation) , chemical physics , globular protein , energy landscape , protein folding , kinetic energy , transition state , contact order , molecular dynamics , native state , computational chemistry , physics , classical mechanics , demography , sociology , computer science , programming language , catalysis , biochemistry , electrical engineering , engineering
The protein folding process is described by a cluster model based on the assumption that local structures or clusters are formed at an early stage in different regions of the polypeptide chain. Possible local structural elements in a globular protein are helices, bends, and hydrophobic cores whose formation is presumably determined by the interaction with the environment. Thus the tendency of local structure formation is expressed by a surface free energy of the cluster, which is assigned to the interface between the cluster and its environment. The probability of finding the chain of N residues with k clusters and m residues in the cluster is represented by a cluster distribution map. The cluster model exhibits a distinct two‐state‐like equilibrium transition, which can be seen on this map as well‐separated native and denatured populations at the midpoint of the transition. The native population is localized at k ≈ 1 and m ≈ N , while the position of the denatured population can vary significantly depending on the surface free energy of the cluster. If the surface free energy is strong, the denatured population is localized near k = 0 and m = 0. On the other hand, if the surface free energy is weak, the denatured population is localized at high k and m values. The dynamics of the cluster model are treated as a stochastic process involving the transition from a state ( k , m ) to one of its six neighbors. The transition probability for each transition is determined by the free energy difference between two states; thus no activation process is assumed. However, the conversion of the two macrostates, native and denatured populations, involves the free energy activation due to the cooperative interaction of the macrosystem. The dynamics are analyzed by following the time evolution of the population profile on the cluster distribution map. Kinetic schemes are proposed to describe the multistep mechanism of protein folding and unfolding.