A MOLECULAR MECHANICS GRID METHOD FOR EVALUATION OF LIGAND-RECEPTOR INTERACTIONS
A MOLECULAR MECHANICS GRID METHOD FOR EVALUATION OF LIGAND-RECEPTOR INTERACTIONS
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DOI：
10.1002/jcc.540160409
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发表时间：
1995-04-01
影响因子：
3
通讯作者：
MCCAMMON, JA
中科院分区：
文献类型：
--
作者：
LUTY, BA;WASSERMAN, ZR;MCCAMMON, JA
我们提出了一个计算方法预测的构象时，结合到一个大分子受体的配体。该方法预期用于结合位点的大致位置已知且预期在复合物形成时不会发生受体大规模重排的系统。配体最初被放置在结合位点附近，并且配体和结合位点的原子运动被明确地模拟，溶剂由隐式溶剂化模型表示，并且使用受体蛋白质的大部分的网格表示。这两个近似使得该方法计算效率高，但仍保持接近全原子计算的精度。对于苯甲脒/胰蛋白酶系统，我们运行了100个独立的模拟，在其中许多配体解决到低能量构象中观察到的复杂的晶体结构。这些构象的能量低于其他样品的能量，并且与其他样品的能量分离良好。本文还讨论了该方法的推广。(C)1995年，John Wiley and Sons，Inc.
We present a computational method for prediction of the conformation of a ligand when bound to a macromolecular receptor. The method is intended for use in systems in which the approximate location of the binding site is known and no large-scale rearrangements of the receptor are expected upon formation of the complex. The ligand is initially placed in the vicinity of the binding site and the atomic motions of the ligand and binding site are explicitly simulated, with solvent represented by an implicit solvation model and using a grid representation for the bulk of the receptor protein. These two approximations make the method computationally efficient and yet maintain accuracy close to that of an all-atom calculation. For the benzamidine/trypsin system, we ran 100 independent simulations, in many of which the ligand settled into the low-energy conformation observed in the crystal structure of the complex. The energy of these conformations was lower than and well-separated from that of others sampled. Extensions of this method are also discussed. (C) 1995 by John Wiley and Sons, Inc.