Relative pKa values from first-principles molecular dynamics:: The case of histidine deprotonation
Relative pKa values from first-principles molecular dynamics:: The case of histidine deprotonation
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DOI：
10.1021/jp056750i
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发表时间：
2006-03-30
影响因子：
3.3
通讯作者：
Klein, ML
中科院分区：
文献类型：
--
作者：
Ivanov, I;Chen, B;Klein, ML
精确计算凝聚相中酸碱反应的pK（a）值和自由能一直是理论化学的目标。我们提出了一个新的应用的Car-Parrinello分子动力学方法的问题，相对pK（a）的测定。作为一个特殊的例子，我们专注于组氨酸解离的第二阶段，这是一个对生物学特别重要的过程。利用约束分子动力学，我们分析了结构，电子和动力学transformatio我们发生沿着一个预选的，直观的反应坐标。通过对组氨酸去质子化和参考反应水自解离的平均力势进行积分，我们得到pK（a）值为6.8，这似乎与实验估计值6.1非常一致。进行详细分析以确定约束的值，该约束将N*-H* 从共价键转化为氢键。这有助于确定一些可以成功地用于监测解离过程的特性。在电子定位功能方面的额外分析提供了有价值的洞察性质的去质子化反应。
Accurate calculation of pK(a) values and free energies for acid/base reactions in the condensed phase has been a long-standing goal of theoretical chemistry. We present a novel application of the Car-Parrinello molecular dynamics method to the problem of relative pK(a) determination. As a particular example, we focus on the second stage in the dissociation of histidine, a process that holds special importance for biology. Using constrained molecular dynamics, we have analyzed the structural, electronic, and dynamical trans formatio us taking place along a preselected, intuitive reaction coordinate. By integrating the potentials of mean force for the deprotonation of histidine and for a reference reaction, autodissociation of water, we obtain a pK(a) value of 6.8, which appears to be in good agreement with the experimental estimate of 6.1. Detailed analysis was undertaken to determine the value of the constraint, which transformed the N*-H* from a covalent to a hydrogen bond. This helped to identify a number of properties that could be successfully used in monitoring the dissociation process. Additional analysis in terms of electron localization functions provided valuable insight into the nature of the deprotonation reaction.