Group Additivity in Ligand Binding Affinity: An Alternative Approach to Ligand Efficiency,Journal of Chemical Information and Modeling

当前位置： X-MOL 学术 › J. Chem. Inf. Model. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Group Additivity in Ligand Binding Affinity: An Alternative Approach to Ligand Efficiency
Journal of Chemical Information and Modeling ( IF 5.6 ) Pub Date : 2017-11-16 00:00:00 , DOI: 10.1021/acs.jcim.7b00381
Charles H. Reynolds ₁ , Ryan C. Reynolds ₁

Affiliation

Group additivity is a concept that has been successfully applied to a variety of thermochemical and kinetic properties. This includes drug discovery, where functional group additivity is often assumed in ligand binding. Ligand efficiency can be recast as a special case of group additivity where ΔG/HA is the group equivalent (HA is the number of non-hydrogen atoms in a ligand). Analysis of a large data set of protein–ligand binding affinities (K_i) for diverse targets shows that in general ligand binding is distinctly nonlinear. It is possible to create a group equivalent scheme for ligand binding, but only in the context of closely related proteins, at least with regard to size. This finding has broad implications for drug design from both experimental and computational points of view. It also offers a path forward for a more general scheme to assess the efficiency of ligand binding.

中文翻译：

配体结合亲和力中的基团加性：配体效率的另一种方法。

基团可加性是已成功应用于多种热化学和动力学性质的概念。这包括药物发现，通常在配体结合中假定官能团可加性。配体效率可以作为基团加和的特例进行重塑，其中ΔG / HA是基团当量（HA是配体中非氢原子的数目）。大量蛋白质-配体结合亲和力数据分析（K _i）对于不同的靶标显示，通常配体结合明显是非线性的。可以创建用于配体结合的基团等效方案，但仅在紧密相关的蛋白质的情况下，至少在大小方面。从实验和计算的角度来看，这一发现对药物设计具有广泛的意义。它还为评估配体结合效率的更通用的方案提供了一条途径。

更新日期：2017-11-17

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11