Department of Chemical Engineering, Princeton University, Princeton, NJ 08544, USA.
Curr Drug Targets. 2010 Mar;11(3):264-78. doi: 10.2174/138945010790711914.
This paper provides an overview of computational de novo protein design methods, highlighting recent advances and successes. Four protein systems are described that are important targets for drug design: human immunodeficiency virus 1, purine nucleoside phosphorylase, ubiquitin specific protease 7, and histone demethylases. Target areas for drug design for each protein are described, along with known inhibitors, focusing on peptidic inhibitors, but also describing some small-molecule inhibitors. Computational design methods that have been employed in elucidating these inhibitors for each protein are outlined, along with steps that can be taken in order to apply computational protein design to a system that has mainly used experimental methods to date.
本文概述了计算从头设计蛋白质的方法，重点介绍了最近的进展和成功。描述了四个对药物设计很重要的蛋白质系统：人类免疫缺陷病毒 1、嘌呤核苷磷酸化酶、泛素特异性蛋白酶 7 和组蛋白去甲基酶。描述了每个蛋白质的药物设计目标区域，以及已知的抑制剂，重点介绍了肽类抑制剂，但也描述了一些小分子抑制剂。概述了为每个蛋白质阐明这些抑制剂所采用的计算设计方法，以及为一个迄今为止主要使用实验方法的系统应用计算蛋白质设计可以采取的步骤。
