Computer-aided design of non-nucleoside inhibitors of HIV-1 reverse transcriptase
Computer-aided design of non-nucleoside inhibitors of HIV-1 reverse transcriptase
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DOI：
10.1016/j.bmcl.2005.10.038
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发表时间：
2006-02-01
影响因子：
2.7
通讯作者：
Hamilton, AD
中科院分区：
文献类型：
--
作者：
Jorgensen, WL;Ruiz-Caro, J;Hamilton, AD
描述了 HIV-1 逆转录酶 (NNRTI) 非核苷抑制剂的设计原则。同时优化野生型 RT 的结合亲和力、病毒突变的耐受性和物理特性。其特色包括使用不断增长的程序 BOMB 进行自动先导生成、使用自由能扰动理论进行先导优化的蒙特卡洛模拟以及使用 QikProp 进行属性分析。最初的 30 μM 引线已快速优化至 10 nM 水平。 (c) 2005 Elsevier Ltd. 保留所有权利。
Design principles are delineated for non-nucleoside inhibitors for HIV-1 reverse transcriptase (NNRTIs). Simultaneous optimization of binding affinity for wild-type RT, tolerance for viral mutations, and physical properties is pursued. Automated lead generation with the growing program BOMB, Monte Carlo simulations with free-energy perturbation theory for lead optimization, and property analysis with QikProp are featured. An initial 30 mu M lead has been optimized rapidly to the 10 nM level. (c) 2005 Elsevier Ltd. All rights reserved.