Cheeseright Tim, Mackey Mark, Rose Sally, Vinter Andy
Cresset Biomolecular Discovery Ltd., Spirella Building, Letchworth, Hertfordshire SG6 1ET, United Kingdom.
J Chem Inf Model. 2006 Mar-Apr;46(2):665-76. doi: 10.1021/ci050357s.
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.
该论文描述了四种三维分子场描述符或“场点”的生成，这些描述符是静电场、立体场和疏水场的极值。这些场点用于定义分子以特定方式结合到指定活性位点所需的性质。其假设是，无论结构如何，显示相似场点模式的化合物可能在同一靶点结合。使用HIV非核苷逆转录酶抑制剂（NNRTI）和凝血酶配体说明了测试这一想法的方法，并在其他七个靶点上进行了验证。通过场点叠加的计算机模拟比较，可以从成对比较中重现这些配体在各自位点的实验观察到的结合姿势。
