α-helix formation:: Discontinuous molecular dynamics on an intermediate-resolution protein model

被引:156
作者
Smith, AV [1 ]
Hall, CK [1 ]
机构
[1] N Carolina State Univ, Dept Chem Engn, Raleigh, NC 27695 USA
关键词
helix-coil transition; computer simulation; four-bead protein model;
D O I
10.1002/prot.1100
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
An intermediate-resolution model of small, homogeneous peptides is introduced, and discontinuous molecular dynamics simulation is applied to study secondary structure formation. Physically, each model residue consists of a detailed three-bead backbone and a simplified single-bead side-chain. Excluded volume and hydrogen bond interactions are constructed with discontinuous (i.e., hard-sphere and square-well) potentials. Simulation results show that the backbone motion of the model is limited to realistic regions of Phi-Psi conformational space. Model polyalanine chains undergo a locally cooperative transition to form a-helices that are stabilized by backbone hydrogen bonding, while model polyglycine chains tend to adopt nonhelical structures. When side-chain size is increased beyond a critical diameter, steric interactions prevent formation of long a-helices. These trends in helicity as a function of residue type have been well documented by experimental, theoretical, and simulation studies and demonstrate the ability of the intermediate-resolution model developed in this work to accurately mimic realistic peptide behavior. The efficient algorithm used permits observation of the complete helix-coil transition within 15 min on a single-processor workstation, suggesting that simulations of very long times are possible with this model. (C) 2001 Wiley-Liss, Inc.
引用
收藏
页码:344 / 360
页数:17
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