Molecular field extrema as descriptors of biological activity: Definition and validation
Molecular field extrema as descriptors of biological activity: Definition and validation
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DOI：
10.1021/ci050357s
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发表时间：
2006-03-01
影响因子：
5.6
通讯作者：
Vinter, A
中科院分区：
文献类型：
--
作者：
Cheeseright, T;Mackey, M;Vinter, A
本文描述了四种类型的三维分子场描述符或‘场点’的产生，它们是静电场、立体场和疏水场的极值。这些场点用于定义分子以一种特有的方式结合到特定活性部位所需的性质。假设显示相似场点模式的化合物可能结合在相同的靶点上，而不考虑结构。使用HIV NNRTI和凝血酶配体说明了测试这一想法的方法，并在其他七个目标上进行了验证。从场点覆盖的电子比较中，这些配体在其各自位置上的实验观察到的结合姿势可以通过成对比较来再现。
The paper describes the generation of four types of three-dimensional molecular field descriptors or 'field points' as extrema of electrostatic, steric, and hydrophobic fields. These field points are used to define the properties necessary for a molecule to bind in a characteristic way into a specified active site. The hypothesis is that compounds showing a similar field point pattern are likely to bind at the same target site regardless of structure. The methodology to test this idea is illustrated using HIV NNRTI and thrombin ligands and validated across seven other targets. From the in silico comparisons of field point overlays, the experimentally observed binding poses of these ligands in their respective sites can be reproduced from pairwise comparisons.