Coupling between conformation and proton binding in proteins.
Coupling between conformation and proton binding in proteins.
复制标题
蛋白质中构象与质子结合之间的耦合。
DOI：
10.1002/prot.20531
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发表时间：
2005
期刊：
影响因子：
2.9
通讯作者：
Scheraga,HaroldA
中科院分区：
文献类型：
--
作者：
Vila,JorgeA;Ripoll,DanielR;Arnautova,YelenaA;Vorobjev,YuryN;Scheraga,HaroldA
这里的兴趣集中在使用蛋白质溶质的固定电荷分布，或通过求解泊松方程考虑质子结合平衡的处理，是否是区分蛋白质天然构象和非天然构象的更好方法。在7种蛋白质的电荷分布的分析中，我们通过探索整个分子的2种可能的电离状态来估计溶剂化自由能对总自由能的贡献，其中，2种可能的电离状态是氨基酸序列中可电离基团的数量，对于7种蛋白质的集合中的每个构象。作为静电相互作用在确定天然折叠的电荷分布中的作用的额外考虑，我们对一组21个天然样蛋白中的可电离残基的替代电荷分配模型进行了比较。这项工作的结果表明，（1）对于7种蛋白质中的6种，基于具有固定电荷分布的广义Born模型的溶剂极化估计提供了精确度（相对于泊松方程）和速度（与可及表面积模型相比）之间的最佳权衡;对于第七种蛋白质，考虑整个分子的所有可能的电离状态似乎是区分天然构象和非天然构象的关键;（2）不同电荷模型的天然折叠电离度和电荷分布存在显著差异;（3）天然状态的稳定性由所有能量分量的微妙平衡决定，以及（4）构象熵，因此折叠的动力学，可能对成功的从头计算蛋白质折叠预测起着至关重要的作用。Proteins 2005.© 2005 Wiley利斯公司
Interest centers here on whether the use of a fixed charge distribution of a protein solute, or a treatment that considers proton‐binding equilibria by solving the Poisson equation, is a better approach to discriminate native from non‐native conformations of proteins. In this analysis of the charge distribution of 7 proteins, we estimate the solvation free energy contribution to the total free energy by exploring the 2ζpossible ionization states of the whole molecule, with ζ being the number of ionizable groups in the amino acid sequence, for every conformation in the ensembles of 7 proteins. As an additional consideration of the role of electrostatic interactions in determining the charge distribution of native folds, we carried out a comparison of alternative charge assignment models for the ionizable residues in a set of 21 native‐like proteins. The results of this work indicate that (1) for 6 out of 7 proteins, estimation of solvent polarization based on the Generalized Born model with a fixed charge distribution provides the optimal trade‐off between accuracy, with respect to the Poisson equation, and speed when compared to the accessible surface area model; for the seventh protein, consideration ofallpossible ionization states of the whole molecule appears to be crucial to discriminate the native from non‐native conformations; (2) significant differences in the degree of ionization and hence the charge distribution for native folds are found between the different charge models examined; (3) the stability of the native state is determined by a delicate balance ofallthe energy components, and (4) conformational entropy, and hence the dynamics of folding, may play a crucial role for a successful ab initio protein folding prediction. Proteins 2005. © 2005 Wiley‐Liss, Inc.