MOLECULAR-DYNAMICS STUDIES OF A DNA-BINDING PROTEIN .2. AN EVALUATION OF IMPLICIT AND EXPLICIT SOLVENT MODELS FOR THE MOLECULAR-DYNAMICS SIMULATION OF THE ESCHERICHIA-COLI TRP REPRESSOR
MOLECULAR-DYNAMICS STUDIES OF A DNA-BINDING PROTEIN .2. AN EVALUATION OF IMPLICIT AND EXPLICIT SOLVENT MODELS FOR THE MOLECULAR-DYNAMICS SIMULATION OF THE ESCHERICHIA-COLI TRP REPRESSOR
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DOI：
10.1002/pro.5560010912
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发表时间：
1992-09-01
期刊：
影响因子：
8
通讯作者：
KOLLMAN, PA
中科院分区：
文献类型：
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作者：
GUENOT, J;KOLLMAN, PA
尽管具有周期性边界条件的水模拟比真空模拟更准确地描述了蛋白质动力学，但对于大多数蛋白质来说，这些模拟的计算量很大。启动模型周围有一个小水壳的色氨酸抑制因子动态模拟产生的蛋白质轨迹比气相有明显改善，但计算效率很高。在分子动力学模拟中，明确的水通过对抗不对称的蛋白质蛋白质力来维持蛋白质亲水原子的表面暴露和疏水原子的埋藏。这可以正确地定位蛋白质表面侧链，减少蛋白质波动，并降低晶体结构的总体均方根偏差。对于仅含晶体水的模拟，线性或s型距离相关的介电模型比常数介电模型产生更好的轨迹。随着越来越多的水加入到初始模型中，使用距离相关和常数介电模型之间的差异变得越来越小，尽管线性距离相关的介电产生的平均结构比常数介电模型更接近晶体结构。对于线性距离相关的介电模拟，大于1的乘法常数产生的轨迹在描述色散抑制因子动力学方面逐渐变差。模拟牛胰蛋白酶，以确保trp抑制因子的结果不依赖于蛋白质，并探索非键切断对距离依赖和恒定介电模拟模型的影响。非键切断显著影响恒定但不依赖距离的介电牛胰蛋白酶抑制剂模拟。与trp抑制因子一样，与距离相关的介电模型（蛋白质周围有一层水）比恒定介电模型产生的轨迹更符合晶体结构，并且轨迹平均结构的物理性质，无论有无键切断，都是相似的。
Although aqueous simulations with periodic boundary conditions more accurately describe protein dynamics than in vacuo simulations, these are computationally intensive for most proteins. Trp repressor dynamic simulations with a small water shell surrounding the starting model yield protein trajectories that are markedly improved over gas phase, yet computationally efficient. Explicit water in molecular dynamics simulations maintains surface exposure of protein hydrophilic atoms and burial of hydrophobic atoms by opposing the otherwise asymmetric protein-protein forces. This properly orients protein surface side chains, reduces protein fluctuations, and lowers the overall root mean square deviation from the crystal structure. For simulations with crystallographic waters only, a linear or sigmoidal distance-dependent dielectric yields a much better trajectory than does a constant dielectric model. As more water is added to the starting model, the differences between using distance-dependent and constant dielectric models becomes smaller, although the linear distance-dependent dielectric yields an average structure closer to the crystal structure than does a constant dielectric model. Multiplicative constants greater than one, for the linear distance-dependent dielectric simulations, produced trajectories that are progressively worse in describing trp repressor dynamics. Simulations of bovine pancreatic trypsin were used to ensure that the trp repressor results were not protein dependent and to explore the effect of the nonbonded cutoff on the distance-dependent and constant dielectric simulation models. The nonbonded cutoff markedly affected the constant but not distance-dependent dielectric bovine pancreatic trypsin inhibitor simulations. As with trp repressor, the distance-dependent dielectric model with a shell of water surrounding the protein produced a trajectory in better agreement with the crystal structure than a constant dielectric model, and the physical properties of the trajectory average structure, both with and without a nonbonded cutoff, were comparable.