Calculations of proton-binding thermodynamics in proteins.
Calculations of proton-binding thermodynamics in proteins.
复制标题
蛋白质中质子结合热力学的计算。
DOI：
10.1016/s0076-6879(98)95040-6
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发表时间：
1998
影响因子：
--
通讯作者：
Case,DA
中科院分区：
文献类型：
--
作者：
Beroza,P;Case,DA
质子结合的计算模型可以从化学复杂和统计简单（如在量子计算中）到化学简单和统计复杂。多位点滴定问题的研究取得了很大进展。在质子结合的几何形状和与滴定相关的更大规模的蛋白质运动方面，计算有了更大的灵活性。本文集中讨论当前计算的原理，但不试图考察它们的定量性能。这是(1)因为在引用的论文中给出了这样的比较，(2)因为在理解构象灵活性和相互作用能方面的持续发展将需要开发具有强大预测能力的稳健方法。然而，过去几年取得的进展不应被低估：质子化行为及其与构象变化耦合的严肃计算，现在可以在对这种模型的优势和局限性日益了解的背景下自信地进行。希望这样的理论进展也将激发新的实验兴趣，测量整体滴定曲线和单个pKa值或pKa位移。探索单个滴定曲线的形状（由希尔系数和其他参数测量）对于评估计算的准确性和绘制与功能行为的联系也很有用。
Computational models of proton binding can range from the chemically complex and statistically simple (as in the quantum calculations) to the chemically simple and statistically complex. Much progress has been made in the multiple-site titration problem. Calculations have improved with the inclusion of more flexibility in regard to both the geometry of the proton binding and the larger scale protein motions associated with titration. This article concentrated on the principles of current calculations, but did not attempt to survey their quantitative performance. This is (1) because such comparisons are given in the cited papers and (2) because continued developments in understanding conformational flexibility and interaction energies will be needed to develop robust methods with strong predictive power. Nevertheless, the advances achieved over the past few years should not be underestimated: serious calculations of protonation behavior and its coupling to conformational change can now be confidently pursued against a backdrop of increasing understanding of the strengths and limitations of such models. It is hoped that such theoretical advances will also spur renewed experimental interest in measuring both overall titration curves and individual pKa values or pKa shifts. Exploration of the shapes of individual titration curves (as measured by Hill coefficients and other parameters) would also be useful in assessing the accuracy of computations and in drawing connections to functional behavior.