Acta Chimica Sinica ›› 2011, Vol. 69 ›› Issue (05): 515-522.

Full Papers

### 基于配体、受体和复合物指纹的虚拟筛选方法比较

1. (同济大学生命科学与技术学院 上海 200092)
• 投稿日期:2010-11-10 修回日期:2010-12-02 发布日期:2010-12-13
• 通讯作者: 朱瑞新 E-mail:rxzhu@tongji.edu.cn

### Comparison of Ligand-, Target Structure-, and Protein-Ligand Interaction Fingerprint-based Virtual Screening Methods

HUANG Qi, KANG Hong, ZHANG Duan-Feng, SHENG Zhen, LIU Qi, ZHU Rui-Xin, CAO Zhi-Wei

1. (School of Life Sciences and Technology, Tongji University, Shanghai 200092)
• Received:2010-11-10 Revised:2010-12-02 Published:2010-12-13

Nowadays, as the supplementary of ligand- and target structure-based methods, the Protein-ligand interaction fingerprint-based drug virtual screening methods have attracted more and more attentions. Does such novel method have advantage in improving the screening accuracy compared with the traditional ones? Also, since the interaction fingerprints can be obtained from the co-crystallized X-ray or molecular docking, is the screening difference based on such two interaction fingerprints significant enough? In this paper, a set of X-ray structures of HIV-1 protease complexes are used to compare the ranking results achieved by the similarity comparison based on four kinds of scorings, i.e., docking energy score, interaction fingerprints score from X-ray structures as well as molecular docking poses, and finally the molecular fingerprints score. It is clearly shown that (i) when the X-ray structures were used, the quality of ranking by docking energy score or similarity of interaction fingerprints outperforms that by molecular fingerprints, due to that the target structure information and ligand information are all taken into consideration|(ii) Normally in ordinary applications, since it is not feasible to co-crystallize all structures, the complex structures are predicted by molecular docking and then the fingerprints of the complex are generated. Our study indicated that there is no significant statistically difference between the screening results evaluated by interaction fingerprints scores obtained from the docking poses and the X-ray complex structures. Thus it can be served as an efficient drug virtual screen method complement to the experimental based interaction fingerprints method.