Docking and CoMFA study on novel human CCR5 receptor antagonists

The CC-chemokine receptor 5 (CCR5), a membrane protein belonging to the G protein-coupled receptor super-family, has been identified as an essential co-receptor for HIV entry into the cells. Small molecules were used to inhibit HIV entry by targeting CCR5. In this study, comparative molecular field analysis (CoMFA) was carried out on 70 novel phenoxybenzyl derivatives as antagonists of CCR5 HIV co receptor. This CoMFA model yielded satisfactory statistical data with the cross-validated q2 of 0.611 and non-cross-validated r2 of 0.903. Mapping this model according to the topology of the active site of CCR5 end to a better understanding of antagonist-CCR5 interactions. Because of lacking crystallography structure of CCR5, the 3D structure from threading assembly refinement (TASSER) method was used. These antagonists were docked into the binding site of the 3D model of CCR5 using ligandfit, and the probable interaction model between CCR5 and the antagonists were obtained. The correlation of predicted binding affinities between antagonists and CCR5 has good statistical quality.