Coupling between folding and ionization equilibria: Effects of pH on the conformational preferences of polypeptides
Coupling between folding and ionization equilibria: Effects of pH on the conformational preferences of polypeptides
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DOI：
10.1006/jmbi.1996.0676
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发表时间：
1996-12-13
影响因子：
5.6
通讯作者：
Scheraga, HA
中科院分区：
文献类型：
--
作者：
Ripoll, DR;Vorobjev, YN;Scheraga, HA
提出了一种研究多肽构象的新方法。它明确地考虑了分子构象与给定pH值下的电离平衡之间的耦合。用快速多重网格边界元方法(MBE)计算了17个残基多肽的溶剂化自由能和电离自由能。MBE方法采用非规则边界元对分子表面进行自适应剖分，快速求解泊松方程，具有较高的精度。将MBE方法结合到ECEPP(ECEPP)算法中，计算了分子的电离态和构象之间的耦合，并用这种方法研究了一种短的多肽的构象偏好，核磁共振和CD实验数据表明，在低pH值下，含有右旋α-螺旋链段的构象在能量上是有利的。与以前使用标准技术(在每个pH下使用预先分配的电荷)不能重现实验结果相比，使用本方法的计算结果与实验非常吻合。此外，还显示了在任何给定的pH下，与构象的偶联如何导致给定类型的残基，例如谷氨酸，在氨基酸序列中的不同位置发生不同程度的电离。本研究结果为探讨多肽构象稳定性的来源及其与环境条件的依赖关系提供了良好的依据。(C)1996年学术出版社有限公司
A new approach to the conformational study of polypeptides is presented. It considers explicitly the coupling between the conformation of the molecule and the ionization equilibria at-a given pH value. Calculations of the solvation free energy and free energy of ionization of a 17-residue polypeptide are carried out using a fast multigrid boundary element method (MBE). The MBE method uses an adaptive tessellation of the molecular surface by boundary elements with non-regular size to solve the Poisson equation rapidly, and with a high degree of accuracy. The MBE method is integrated into the ECEPP (Empirical Conformational Energy Program for Peptides) algorithm to compute the coupling between the ionization state and the conformation of the molecule.This approach has been applied to study the conformational preference of a short polypeptide for which the available NMR and CD experimental data indicate that conformations containing a right-handed alpha-helical segment are energetically moro favorable at low values of pH. The results of calculations using the present method agree quite well with experiments, in contrast to previous applications with standard techniques (using pre-assigned charges at each pH) that were not able to reproduce the experimental findings. Also, it is shown how the coupling to the conformation leads to different degrees of ionization of a given type of residue, for example glutamic acid, at-different positions in the amino acid sequence, at any given pH. The results of this study provide a sound basis to discuss the origin of the stability of polypeptide conformations, and its dependence on the environmental conditions. (C) 1996 Academic Press Limited