Further development of hydrogen bond functions for use in determining energetically favorable binding sites on molecules of known structure. 1. Ligand probe groups with the ability to form two hydrogen bonds.
Further development of hydrogen bond functions for use in determining energetically favorable binding sites on molecules of known structure. 1. Ligand probe groups with the ability to form two hydrogen bonds.
复制标题
进一步开发氢键功能，用于确定已知结构分子上有利的能量结合位点。
DOI：
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发表时间：
1993
影响因子：
7.3
通讯作者：
P. Goodford
中科院分区：
文献类型：
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作者：
R. Wade;K. Clark;P. Goodford
氢键的定向性质在确定分子间相互作用的特异性方面起着重要作用。一个明确考虑这些性质的能量函数已经被开发出来，用于通过GRID方法确定已知结构分子上的能量有利配体结合位点（Goodford， P.J.J. Med. Chem. 1985, 28,849）。Boobbyer D.N.A.;Goodford P.J.;McWhinnie点;Wade， R.C.J.医学化学。1989,32,1083)。在这种方法中，目标分子和一个小的化学基团（探针）之间的相互作用能，可能是一个更大的配体的一部分，是用一个由Lennard-Jones、静电和氢键项组成的能量函数来计算的。后一项是氢键长度的函数，它在氢键原子上的取向，以及它们的化学性质。我们现在描述氢键能量函数，该函数考虑了具有形成两个氢键能力的探针所形成的氢键的空间分布。设计这些函数是为了模拟实验中观察到的氢键的角依赖性。我们还描述了确定相互作用能最优的探针位置和方向的过程。生物学和药理学研究的例子证明了这种方法的应用，表明它可以产生与其他理论方法和实验观察一致的结果。
The directional properties of hydrogen bonds play a major role in determining the specificity of intermolecular interactions. An energy function which takes explicit account of these properties has been developed for use in the determination of energetically favorable ligand binding sites on molecules of known structure by the GRID method (Goodford, P.J.J. Med. Chem. 1985, 28, 849. Boobbyer, D.N.A.; Goodford, P.J.; McWhinnie, P.M.; Wade, R.C.J. Med. Chem. 1989, 32, 1083). In this method, the interaction energy between a target molecule and a small chemical group (a probe), which may be part of a larger ligand, was calculated using an energy function consisting of Lennard-Jones, electrostatic, and hydrogen bond terms. The latter term was a function of the length of the hydrogen bond, its orientation at the hydrogen-bonding atoms, and their chemical nature. We now describe hydrogen bond energy functions which take account of the spatial distribution of the hydrogen bonds made by probes with the ability to form two hydrogen bonds. These functions were designed so as to model the experimentally observed angular dependence of the hydrogen bonds. We also describe the procedure to locate the position and orientation of the probe at which the interaction energy is optimized. The use of this procedure is demonstrated by examples of biological and pharmacological interest which show that it can produce results that are consistent with other theoretical approaches and with experimental observations.