Automated Ligand- and Structure-Based Protocol for in Silico Prediction of Human Serum Albumin Binding

作者：Hall Michelle Lynn; Jorgensen William L; Whitehead Lewis^*

来源：Journal of Chemical Information and Modeling, 2013, 53(4): 907-922.

DOI：10.1021/ci3006098

Plasma protein binding has a profound impact on the pharmacokinetic and pharmacodynamic properties of many drug candidates and is thus an integral component of drug discovery. Nevertheless, extant methods to examine small-molecule interactions with plasma protein have various limitations, thus creating a need for alternative methods. Herein we present a comprehensive and cross-validated in silico workflow for the prediction of small-molecule binding to Human Serum Albumin (HSA), the most ubiquitous plasma protein. This protocol reliably predicts small-molecule interactions with HSA, including a binding affinity calculation using multiple linear regression methods, binding site prediction using a naive-Bayes classifier, and a three-dimensional binding pose using induced fit docking. Furthermore, this workflow is implemented in a portable and automated format that can be downloaded and used by other end users, either as is or with customization.

• 出版日期2013-4