Clark D E, Frenkel D, Levy S A, Li J, Murray C W, Robson B, Waszkowycz B, Westhead D R
Proteus Molecular Design Ltd., Macclesfield, Cheshire, U.K.
J Comput Aided Mol Des. 1995 Feb;9(1):13-32. doi: 10.1007/BF00117275.
An approach to de novo molecular design, PRO-LIGAND, has been developed that, in the environment of a large, integrated molecular design and simulation system, provides a unified framework for the generation of novel molecules which are either similar or complementary to a specified target. The approach is based on a methodology that has proved to be effective in other studies--placing molecular fragments upon target interaction sites-but incorporates many novel features such as the use of a rapid graph-theoretical algorithm for fragment placing, a generalised driver for structure generation which offers a large variety of fragment assembly strategies to the user and the pre-screening of library fragments. After a detailed description of the relevant modules of the package, PRO-LIGAND's efficacy in aiding rational drug design is demonstrated by its ability to design mimics of methotrexate and potential inhibitors for dihydrofolate reductase and HIV-1 protease.
一种全新的分子设计方法——PRO-LIGAND已经开发出来，该方法在大型集成分子设计与模拟系统的环境中，为生成与特定靶点相似或互补的新型分子提供了一个统一的框架。该方法基于一种在其他研究中已被证明有效的方法——将分子片段放置在靶点相互作用位点上，但它融入了许多新颖的特性，例如使用快速图论算法进行片段放置、一个用于结构生成的通用驱动程序，该驱动程序为用户提供了多种片段组装策略以及对库片段进行预筛选。在详细描述了该软件包的相关模块之后，通过设计甲氨蝶呤的模拟物以及二氢叶酸还原酶和HIV-1蛋白酶的潜在抑制剂的能力，证明了PRO-LIGAND在辅助合理药物设计方面的功效。
