Water's Contribution to the Energetic Roughness from Peptide Dynamics
Water's Contribution to the Energetic Roughness from Peptide Dynamics
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DOI：
10.1021/ct100183s
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发表时间：
2010-09-01
影响因子：
5.5
通讯作者：
Hamelberg, Donald
中科院分区：
文献类型：
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作者：
Johnson, Quentin;Doshi, Urmi;Hamelberg, Donald
水在蛋白质的动力学和功能中起着非常重要的作用。除了蛋白质与蛋白质水分子的相互作用外，蛋白质运动还伴随着周围水分子氢键网络的形成和断裂。水的这种有序和重新有序也增加了蛋白质能量景观的潜在粗糙度，从而改变了它们的动力学。在这里，我们提取水的贡献的坚固性（在能量尺度0的能量景观从分子动力学模拟脯氨酰顺反异构酶的肽底物类似物。为了做到这一点，我们开发并实现了一个模型的基础上的位置空间模拟的Ornstein-Uhlenbeck过程和Zwanzig的理论扩散的粗糙的潜力。这使我们也可以探测一个重要的属性，广泛使用的原子模拟水模型，直接影响生物分子系统的动力学，并强调了在研究蛋白质动力学的水模型的选择的重要性。我们表明，水有助于额外的粗糙度的能源景观。在较低的温度下，这种粗糙度（与k（B）T相当）可以大大减缓蛋白质动力学。这些结果也有更广泛的影响，某些类别的酶的功能，因为其底物的景观拓扑结构可能会改变后，从水环境中移动到结合位点。
Water plays a very important role in the dynamics and function of proteins. Apart from protein protein and protein water interactions, protein motions are accompanied by the formation and breakage of hydrogen-bonding network of the surrounding water molecules. This ordering and reordering of water also adds to the underlying roughness of the energy landscape of proteins and thereby alters their dynamics. Here, we extract the contribution of water to the ruggedness (in terms of an energy scale 0 of the energy landscape from molecular dynamics simulations of a peptide substrate analogue of prolyl cis-trans isomerases. In order to do so, we develop and implement a model based on the position space analog of the Ornstein-Uhlenbeck process and Zwanzig's theory of diffusion on a rough potential. This allows us to also probe an important property of the widely used atomistic simulation water models that directly affects the dynamics of biomolecular systems and highlights the importance of the choice of the water model in studying protein dynamics. We show that water contributes an additional roughness to the energy landscape. At lower temperatures this roughness, which becomes comparable to k(B)T, can considerably slow down protein dynamics. These results also have much broader implications for the function of some classes of enzymes, since the landscape topology of their substrates may change upon moving from an aqueous environment into the binding site.