Empirical solvation models in the context of conformational energy searches: application to bovine pancreatic trypsin inhibitor.
Empirical solvation models in the context of conformational energy searches: application to bovine pancreatic trypsin inhibitor.
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构象能量搜索背景下的经验溶剂化模型：在牛胰腺胰蛋白酶抑制剂中的应用。
DOI：
10.1002/prot.340140112
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发表时间：
1992
期刊：
影响因子：
2.9
通讯作者：
Scheraga,HA
中科院分区：
文献类型：
--
作者：
Williams,RL;Vila,J;Perrot,G;Scheraga,HA
连续溶剂化模型估计溶剂化的自由能作为溶剂可及表面积的函数，计算简单到足以用于预测蛋白质构象。三个这样的溶剂化模型的行为已被检查，通过将它们应用到牛胰胰蛋白酶抑制剂的构象能的最小化。该模型的不同之处仅在于如何得到的自由能和表面积之间的比例常数。每个模型都是通过拟合实验测得的平衡溶液的性质。对于两种模型，溶液性质为水化自由能。对于第三个，性质是NMR耦合常数。本研究的目的是确定应用这些溶剂化模型的非平衡构象的蛋白质的构象能量最小的全球搜索过程中产生的效果。采用了两种方法：（1）类似于平衡构象的构象系综的局部能量最小化和（2）从类似于平衡构象的单个构象开始使用Monte Carlo加最小化的全局搜索轨迹。结果发现，全局搜索和局部最小化都产生了与X射线晶体学结构更相似的构象，在不存在构象能的溶剂化组分的情况下进行的搜索或局部最小化。来自NMR耦合常数的模型表现出类似于其他模型的背景下，一个全球性的搜索轨迹。对于从测量的水合自由能导出的模型之一，发现近平衡构象的系综的最小化产生了一个新的系综，其中与X射线确定的结构PTI4最相似的构象具有最低的总自由能。在每个模型的轨迹中产生的最终构象表现出一些已经报道的在存在下从分子动力学模拟获得的构象的特征。一个水分子池。他们有较小的均方根（RMS）偏差从实验确定的构象，更少的不正确的氢键，和稍大的回转半径比从搜索轨迹中进行的情况下的sovlent的构象。© 1992 Wiley利斯公司
Continuum solvation models that estimate free energies of solvation as a function of solvent accessible surface area are computationally simple enough to be useful for predicting protein conformation. The behaviour of three such solvation models has been examined by applying them to the minimization of the conformational energy of bovine pancreatic trypsin inhibitor.The model differ only with regard to how the constants of proportionality between free energy and surface area were derived. Each model was derived by fitting to experimentally measured equilibrium solution properties. For two models, the solution property was free energy of hydration. For the thrid, the property was NMR coupling constants. The purpose of this study is to determine the effect of applying these solvation models to the nonequilibrium conformations of a protein arising in the course of global searches for conformational energy minima. Two approaches were used: (1) local energy minimization of an ensemble of conformations similar to the equilibrium conformation and (2) global search trajectories using Monte Carlo plus minimization starting from a single conformation similar to the equilibrium conformation.For the two models derived from free energy measurements, it was found that both the global searches and local minimizations yielded conformations more similar to the X‐ray crystallographic structures than did searches or local minimizations carried out in the absence of a solvation component of the conformational energy. The model derived from NMR coupling constants behaved similarly to the other models in the context of a global search trajectory. For one of the models derived from measured free energies of hydration, it was found that minimization of an ensemble of near‐equilibrium conformations yielded a new ensemble in which the conformation most similar to the X‐ray determined structure PTI4 had the lowest total free energy.Despite the simplicity of the continuum slvation models, the final conformation generated in the trajectories for each of the models exhibited some of the characteristics that have been reported for conformations obtained from molecular dynamics simulations in the presence of a bath of explicit water molecules. They have smaller root mean square (rms) deviations from the experimentally determined conformation, fewer incorrect hydrogen bonds, and slightly larger radii of gyration than do conformations derived from search trajectories carried out in the absence of sovlent. © 1992 Wiley‐Liss, Inc.
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DOI：
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