| 一种新的De Novo生物活性分子设计方法 |
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| 引用本文： | 陈海峰,谷妍,董喜城,荔建锋,张世相,袁身刚,陈敏伯,郑崇直.一种新的De Novo生物活性分子设计方法[J].化学学报,2000,58(9):1168-1172. |
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| 作者姓名： | 陈海峰 谷妍 董喜城 荔建锋 张世相 袁身刚 陈敏伯 郑崇直 |
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| 作者单位： | 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 |
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| 基金项目： | 科技部科技攻关项目，国家重点基础研究发展计划(973计划)，中-法合作项目，国家自然科学基金，国家自然科学基金，教育部留学回国人员科研启动基金，上海市科技开发基金，国家高性能计算基金，，，，，29872048，，，，，，，，，，， |
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| 摘 要： | 由药效团进行虚拟活性结构生成与3D-QSAR模型相结合，筛选出有前途的结构多样性的化合物，并从中寻找活性先导化合物，是一种新的分子设计方法。采用这种方法对抗小麦赤霉病类含氟农药进行了研究，共生成了53个虚拟活性结构，通过3D-QSAR模型筛选出其中10个活性较高的结构，在活性最高的化合物基础上进行了结构修饰，得到了活性更高且毒性较低的理想化合物。研究结果表明这种方法能突破原模型化合物结构模式的局限，可以找到结构新颖的活性先导化合物，是一种非常有前途的分子设计方法，而且具有较高的筛选效率。
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| 关 键 词： | 药效团 分子设计 生物活性 筛选 结构生成 计算机应用 |
| 修稿时间： | 2000年3月27日 |
A new method for De Novo bio-active molecular design |
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| CHEN Hai-feng,GU Yan,DONG Xi-Cheng,LI Jian-Feng,ZHANG Shi-xiang,YUAN Shen-Gang,CHEN Min-Bo,ZHENG Chong-Zhi.A new method for De Novo bio-active molecular design[J].Acta Chimica Sinica,2000,58(9):1168-1172. |
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| Authors: | CHEN Hai-feng GU Yan DONG Xi-Cheng LI Jian-Feng ZHANG Shi-xiang YUAN Shen-Gang CHEN Min-Bo ZHENG Chong-Zhi |
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| Institution: | Shanghai Inst Organ Chem., CAS.Shanghai(200032);Lab of Comp Chem, CAS.Shanghai(200032) |
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| Abstract: | A new De Novo method for bio - active molecular design is presented, which combines virtual bio -active structural generation with 3D - QSAR study. This method could generate a lot of highly diverse molecules and find bio - active lead compounds. The method is illustrated through a study on a set of fluorine - containing pesticides for and - gibberella. With the constraints of the pharmacophore obtained by DISCO, 53 virtual bio - active structures were generated, and their anti - gibberella activities were predicted by CoMFA. The 10 most active compounds were selected and screened by 3D - QSAR. The first one was investigated in depth by modifying and simplifying its structure. The results showed that the method was a feasible means for bio - active molecular design. It had high screen efficiency. |
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| Keywords: | structural generation 3D-QSAR bio - active screen |
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