Folding of proteins with an all-atom Go-model.
Folding of proteins with an all-atom Go-model.
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DOI：
10.1063/1.2943202
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发表时间：
2008-06
期刊：
影响因子：
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通讯作者：
Ling-Zhi Wu;John Z. H. Zhang;M. Qin;Fen Liu;Wei Wang
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文献类型：
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作者：
Ling-Zhi Wu;John Z. H. Zhang;M. Qin;Fen Liu;Wei Wang
在先前的许多工作中，残余水平的go样电位已成功地应用于蛋白质的折叠。然而，考虑到原子水平上更详细的结构信息，这些传统go模型中使用的接触定义可能不适合全原子模拟。在这里，在这项工作中，我们开发了一个合理的定义接触考虑筛选效应在拥挤的分子内环境。与传统定义相比，该方案排除了大量被筛选的原子对，减少了接触次数。这种新定义所定义的这些接触与蛋白质结构的全原子表示相容。为了验证新接触定义的合理性，采用全原子分子动力学方法模拟了蛋白质CI2和SH3的折叠过程。结果表明，该材料具有较高的折叠协同性，且模拟的ph值与实验值具有较好的相关性，特别是对于CI2。这表明，与传统的go模型相比，全原子go模型得到了改进。通过对ph值的比较，讨论了侧链在折叠中的作用，得出了侧链结构对局部接触在决定过渡态结构中的作用更为重要的结论。此外，还讨论了侧链与主链序的关系。
The Go-like potential at a residual level has been successfully applied to the folding of proteins in many previous works. However, taking into consideration more detailed structural information in the atomic level, the definition of contacts used in these traditional Go-models may not be suitable for all-atom simulations. Here, in this work, we develop a rational definition of contacts considering the screening effect in the crowded intramolecular environment. In such a scheme, a large amount of screened atom pairs are excluded and the number of contacts is decreased compared to the case of the traditional definition. These contacts defined by such a new definition are compatible with the all-atom representation of protein structures. To verify the rationality of the new definition of contacts, the folding of proteins CI2 and SH3 is simulated by all-atom molecular dynamics simulations. A high folding cooperativity and good correlation of the simulated Phi-values with those obtained experimentally, especially for CI2, are found. This suggests that the all-atom Go-model is improved compared to the traditional Go-model. Based on the comparison of the Phi-values, the roles of side chains in the folding are discussed, and it is concluded that the side-chain structures are more important for local contacts in determining the transition state structures. Moreover, the relations between side chain and backbone orderings are also discussed.