虚拟活性化合物的自动生成  

Automatic Generation of Virtual Bio - Active Compounds

作　　者：陈海峰[1] 荔建锋[1] 姚建华[1] 袁身刚[1] 郑崇直[1] 

机构地区：[1]中国科学院上海有机化学研究所计算机化学开放实验室,上海200032

出　　处：《化学学报》2000年第5期529-532,共4页Acta Chimica Sinica

基　　金：国家科技部"九五"重点攻关项目(96-547-01-01;96-547-01-02);国家基础研究发展规划(G1998051115);中法先进研究计划(PRA 98M-A036);国家自然科学基金(29832050);国家自然科学基金(29872048);国家教委留学回国人员科研基金;上海市科技开发基金(98BSH1426)

摘　　要：虚拟活性化合物的自动生成是从药效团和预先设定的结构碎片出发,通过碎片选择、碎片组装和柔性构象搜索来获得虚拟活性结构.经过对HIV-1蛋白酶抑制剂药效团进行虚拟活性化合物生成,得到了16个虚拟活性化合物,通过构象分析发现生成的化合物满足药效团的限制条件.说明这一方法能够有效的生成虚拟活性结构,与药效团检索结果对比发现生成的虚拟活性结构新颖易于合成.The described automatic generation of virtual bio - active compounds starts from pharmacophore and pre - selected fragments. The generation process consists of three stages: selection of fragments, assemblage of fragments and conformation flexible searching. This method is demonstrated by an example that sixteen virtual bio - active compounds were generated starting from HIV - 1 protease inhibitors pharmacophore in this work. The results of conformation analysis showed that the pharmacophore is contained in the favorite conformers of the generated structure. It was showed that this method could generate virtual bio - active structure effectively. In comparing of the results from 3D structure searching, the generated structures have novel structural features and they are easier to be synthesized.

关 键 词：虚拟活性化合物 药效团 HIV-1蛋白酶掏剂 

分 类 号：R91[医药卫生—药学]