Critical importance of length-scale dependence in implicit modeling of hydrophobic interactions
Critical importance of length-scale dependence in implicit modeling of hydrophobic interactions
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DOI：
10.1021/ja068383
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发表时间：
2007-03-07
影响因子：
15
通讯作者：
Brooks, Charles L., III
中科院分区：
文献类型：
--
作者：
Chen, Jianhan;Brooks, Charles L., III
疏水溶剂化的长度尺度依赖性的存在对无序、部分折叠和折叠蛋白质构象的平衡具有重要意义。忽略这种依赖性，如在流行的溶质表面积为基础的隐式溶剂模型与固定的表面张力系数，严重限制了准确建模蛋白质构象平衡的能力。我们说明了这样的基本限制，通过检查形成二聚体和三聚体非极性集群的平均力的潜力，并提出了一个新的经验模型，有效地捕捉局部有效表面张力的上下文依赖性。进一步优化的新模型与其他组件的隐式溶剂力场提供了承诺，显着提高一个人的能力，模拟蛋白质折叠和构象转变。
The existence of length-scale dependence of hydrophobic solvation has important implications in the equilibrium of disordered, partially folded, and folded protein conformations. Neglecting this dependence, such as in popular solute surface-area based implicit solvent models with fixed surface tension coefficients, severely limits the ability to accurately model protein conformational equilibrium. We illustrate such fundamental limitations by examining the potentials of mean force of forming dimeric and trimeric nonpolar clusters and propose a new empirical model that effectively captures the context dependence of the local effective surface tension. Further optimization of the new model with other components of the implicit solvent force fields provides promise to significantly improve one's ability to simulate protein folding and conformational transitions.