Modeling the charge distribution at metal sites in proteins for molecular dynamics simulations
Modeling the charge distribution at metal sites in proteins for molecular dynamics simulations
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DOI：
10.1016/j.jsb.2006.10.019
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发表时间：
2007-03-01
影响因子：
3
通讯作者：
Klein, Michael L.
中科院分区：
文献类型：
--
作者：
Dal Peraro, M. D.;Spiegel, Katrin;Klein, Michael L.
生物体中近一半的蛋白质组是由金属蛋白组成的。不幸的是，由于处理极化和电荷转移贡献的内在困难，当前一代分子动力学成对相加力场严重缺乏正确描述金属口袋的能力。为了改善对金属蛋白的描述，本文提出了一种简单的再参数化策略，该策略不涉及人工约束。具体地说，基于非键合量子力学的模型被用来捕捉平均极化和电荷转移对金属位置内原子间作用力的贡献。在扩展的(多纳秒)分子动力学模拟中，本方法被证明提供了足够的准确性来维持各种金属蛋白的金属口袋的完整性。该方法能够采样小的构象变化和放松核磁共振结构中的局部受挫。(C)2006 Elsevier Inc.保留所有权利。
Almost half of the proteome of living organisms is constituted of metalloproteins. Unfortunately, the ability of the current generation of molecular dynamics pairwise-additive forcefields to properly describe metal pockets is severely lacking due to the intrinsic difficulty of handling polarization and charge transfer contributions. In order to improve the description of metalloproteins, a simple reparameterization strategy is proposed herein that does not involve artificial constraints. Specifically, a non-bonded quantum mechanical-based model is used to capture the mean polarization and charge transfer contributions to the interatomic forces within the metal site. The present approach is demonstrated to provide enough accuracy to maintain the integrity of the metal pocket for a variety of metalloproteins during extended (multi-nano second) molecular dynamics simulations. The method enables the sampling of small conformational changes and the relaxation of local frustrations in NMR structures. (c) 2006 Elsevier Inc. All rights reserved.