A computer assisted receptor mapping approach to the design of anti-AIDS agents directed at HIV reverse transcriptase

1993 IEEE Annual Northeast Bioengineering Conference Pub Date : 1993-03-18 DOI:10.1109/NEBC.1993.404373

M. A. Fisher, P. Yadav, J. Yadav, S. Laxminarayan, D. Kristol, M. Modak

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Abstract

The authors take a pharmacophoric approach to the identification of a substrate/inhibitor binding site on HIV-1 RT. A pharmacophore is defined as the spatial arrangement of a set of atoms or groups in a ligand molecule while bound to a given receptor. The pharmacophore's usefulness is in the assumption that a single one exists for a series of compounds binding at the same receptor site. The superposition of a series of substrate and/or inhibitors along a pharmacophoric pattern provides an enzyme excluded volume, which represents a minimum volume requirement for substrate/inhibitors at the receptor binding site. The structure of HIV-1 RT complexed with dsDNA template-primer has been recently described at 7 /spl Aring/ resolution and is currently being extended to 3 /spl Aring/. The combination of crystallographic, pharmacophoric, and existing biochemical and genetic data regarding the substrate binding residues will help to generate an accurate structure of the substrate binding domain of HIV-1 RT and aid in the evaluation of new and specific RT inhibitors.<>

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针对HIV逆转录酶的抗艾滋病药物设计的计算机辅助受体定位方法

作者采用药效团的方法来鉴定HIV-1 rt上的底物/抑制剂结合位点。药效团被定义为与给定受体结合时配体分子中一组原子或基团的空间排列。药效团的有用之处在于假设一系列化合物在同一受体位点结合时存在一个药效团。一系列底物和/或抑制剂沿着药效模式的叠加提供了酶排除体积，这代表了受体结合位点底物/抑制剂的最小体积要求。HIV-1 RT与dsDNA模板引物复合物的结构最近被描述为7 /spl Aring/分辨率，目前正在扩展到3 /spl Aring/分辨率。关于底物结合残基的结晶学、药效学和现有的生化和遗传学数据的结合将有助于生成HIV-1 RT底物结合域的准确结构，并有助于评估新的和特异性的RT抑制剂。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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1993 IEEE Annual Northeast Bioengineering Conference

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