Accurate and efficient description of protein vibrational dynamics: Comparing molecular dynamics and Gaussian models
Accurate and efficient description of protein vibrational dynamics: Comparing molecular dynamics and Gaussian models
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DOI：
10.1002/prot.20049
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发表时间：
2004-05-15
影响因子：
2.9
通讯作者：
Maritan, A
中科院分区：
文献类型：
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作者：
Micheletti, C;Carloni, P;Maritan, A
目前基于全原子电位的分子动力学（MD）允许在大范围的时间尺度上识别蛋白质的功能运动，最高可达几十纳秒。然而，蛋白质的功能性大规模运动可能发生在目前基于全原子势的MD无法实现的时间尺度上。为了避免这种方法所需的大量计算工作量，已经引入了几种简化方案。其中最令人满意的是基于能量扩展的高斯网络方法，该方法基于蛋白质主链偏离其固有构型的偏差。在这里，我们考虑了该模型的扩展，该模型以更现实的方式捕获了由于引入有效侧链质心而产生的本地相互作用的分布。由于它们的位置完全由蛋白质主链决定，因此该模型可以像以前的简单模型一样进行精确且计算效率高的处理。通过一系列成功的比较，该模型能够描述蛋白质残基在热力学平衡中的相关运动，并与基于HIV-1蛋白酶与肽底物复合物的琥珀电位的广泛（14 ns） MD模拟进行了成功的比较。因此，这里提出的模型成为一个强大的工具，提供初步，快速而准确的蛋白质近原生运动特征。(C) 2004 Wiley-Liss, Inc。
Current all-atom potential based molecular dynamics (MD) allows the identification of a protein's functional motions on a wide-range of timescales, up to few tens of nanoseconds. However, functional, large-scale motions of proteins may occur on a timescale currently not accessible by all-atom potential based MD. To avoid the massive computational effort required by this approach, several simplified schemes have been introduced. One of the most satisfactory is the Gaussian network approach based on the energy expansion in terms of the deviation of the protein backbone from its native configuration. Here, we consider an extension of this model that captures in a more realistic way the distribution of native interactions due to the introduction of effective side-chain centroids. Since their location is entirely determined by the protein backbone, the model is amenable to the same exact and computationally efficient treatment as previous simpler models. The ability of the model to describe the correlated motion of protein residues in thermodynamic equilibrium is established through a series of successful comparisons with an extensive (14 ns) MD simulation based on the AMBER potential of HIV-1 protease in complex with a peptide substrate. Thus, the model presented here emerges as a powerful tool to provide preliminary, fast yet accurate characterizations of protein near-native motion. (C) 2004 Wiley-Liss, Inc.