Results of molecular docking as descriptors to predict human serum albumin binding affinity
Results of molecular docking as descriptors to predict human serum albumin binding affinity
复制标题
分子对接结果作为描述符预测人血清白蛋白结合亲和力
DOI：
10.1016/j.jmgm.2011.11.003
复制
发表时间：
2012-03-01
影响因子：
2.9
通讯作者：
Chen, Xin
中科院分区：
文献类型：
--
作者：
Chen, Lijuan;Chen, Xin
化合物的药代动力学特性对于药物发现和开发非常重要。这些性质通常是通过结构活性关系 (QSAR) 方法根据化合物的结构性质来估计的。分子药理学的快速发展已经确定了许多重要蛋白质的特征，这些蛋白质塑造了化合物的药代动力学特征。先前的研究表明，能够分析化合物-蛋白质相互作用的分子对接可用于对药代动力学特性进行分类估计。本研究以人血清白蛋白 (HSA) 的结合亲和力为例，表明对接描述符也可能有助于估计药代动力学特性的准确值。分析了先前报道的包含 94 种具有 log K-HSA 值的化合物的数据集。基于对接描述符的支持向量回归模型能够近似训练和验证数据集中观察到的 log K-HSA，R-2 = 0.79。该精度可与基于复合描述符的已知 QSAR 模型相媲美。在本案例研究中，结果表明，蛋白质灵活性的考虑对于计算用于定量估计 log K-HSA 的信息对接描述符至关重要。 (C) 2011 Elsevier Inc. 保留所有权利。
Pharmacokinetic properties of a compound are important in drug discovery and development. These properties are most often estimated from the structural properties of a compound with a structural-activity relationship (QSAR) approach. Rapid advances in molecular pharmacology have characterized a number of important proteins that shape the pharmacokinetic profile of a compound. Previous studies have shown that molecular docking, which is capable of analyzing compound-protein interactions, could be applied to make a categorical estimation of a pharmacokinetic property. The present study focused on the binding affinity of human serum albumin (HSA) as an example to show that docking descriptors might also be useful to estimate the exact value of a pharmacokinetic property. A previously reported dataset containing 94 compounds with log K-HSA values was analyzed. A support vector regression model based on the docking descriptors was able to approximate the observed log K-HSA in the training and validation dataset with an R-2 = 0.79. This accuracy was comparable to known QSAR models based on compound descriptors. In this case study, it was shown that an account of protein flexibility is essential to calculate informative docking descriptors for use in the quantitative estimation of log K-HSA. (C) 2011 Elsevier Inc. All rights reserved.