Pharmacophore Model Generation Based on Pyrrolidine-and Butane-derived CCR5 Antagonists
In the present study, a three-dimensional pharmacophore model was developed for a great number of pyrrolidine- and butane-based CCR5 antagonists, which block the entry of HIV-1 by inhibiting the interaction of HIV-1 envelope protein and CCR5. The pharmacophore model was generated using a training set consisting of 25 carefully selected antagonists with the diverse molecular architecture and bioactivity, as required by the CATALYST/HypoGen program. The activity of training set molecules expressed in IC50 covered from 0.06 to 10,000 nM. The most predictive pharmacophore model (hypothesis 1), consisting of two positive ionizable points and three hydrophobic, had a correlation of 0.924 and root mean square deviation of 1.067, as well as the cost difference between the null cost and total cost was 63.67 bits. The model was applied in predicting the activity of 244 compounds as test set. The results suggested that the model was able to provided clear guidelines and accurate activity prediction for novel antagonist design.
CCR5 HIV-1 Pharmacophore model ligand based drug design
Ren Kong Xuemei Xu Weizu Chen Cunxin Wang Limin Hu
Laboratory of Molecular design and Bioinformatics, College of Life Sciences and Bioengineering,Beiji Laboratory of Pharmic Chemistry, College of Life Sciences and Bioengineering, Beijing University of
国际会议
杭州
英文
1212-1218
2007-04-01（万方平台首次上网日期，不代表论文的发表时间）