Ligand-docking-based homology model of the melanin-concentrating hormone 1 receptor

ORRY, ANDREW J.; CAVASOTTO, CLAUDIO N.

Washington, DC

Conferencia; 231st National Meeting of the American-Chemical-Society; 2006

A ligand-docking based modeling approach has been developed for GPCRs and applied to the MCH receptor. The final MCH model is shown in Figure 3a and 3b. This model was selected using filters described above and finally the docking analysis shown in Table 1. Table 1 contains the ICM docking data for 23 compounds containing 11 MCH antagonists and their stereoisomers. Using the final model (Final Model 2 in Table 1) the docking results showed that 9 out 11 antagonists were able to dock to the model with good ICM docking scores and most significantly with a H-bond with D3.32. The docking analyis indicates that the model can accommodate a set of MCH antagonists which are structurally diverse and still maintain the key interaction with the aspartate. The final model is suitable for virtual screening and antagonist library design.