DE-NOVO DESIGN OF ENZYME-INHIBITORS BY MONTE-CARLO LIGAND GENERATION

被引：79

作者：

GEHLHAAR, DK

MOERDER, KE

ZICHI, D

SHERMAN, CJ

OGDEN, RC

FREER, ST

机构：

[1] AGOURON PHARMACEUT INC, SAN DIEGO, CA 92121 USA

[2] TORREY SCI & TECHNOL INC, SAN DIEGO, CA 92121 USA

[3] NEXAGEN INC, BOULDER, CO 80301 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1995年 / 38卷 / 03期

关键词：

D O I：

10.1021/jm00003a010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new computational method for the in situ generation of small molecules within the binding site of a protein is described. The method has been evaluated using two well-studied systems, dihydrofolate reductase and thymidylate synthase. The method has also been used to guide improvements to inhibitors of HIV-1 protease. One such improvement resulted in a compound selected for preclinical studies as an antiviral agent against AIDS.

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收藏

页码：466 / 472

页数：7

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