Modeling and docking analysis of GPR87 with anti-cancer drugs

Abstract

Orphan G-protein coupled receptor 87 (GPR87) in human is a very recently discovered orphan GPCR means that the search for their endogenous ligands has been a challenge. GPR87 was shown to be over expressed in squamous cell carcinoma (SCCs) or adenocarcinoma in the lung and bladder carcinomas. We have predicted the comparative account on 3Dstructures of GPR87 on the basis of PDB ID: 3ODU|A. The model was further validated by comparison with structural features of the template proteins by using Verify-3D,ProSA and ERRAT servers were used for determining the stereo-chemical parameters of 3D structure of GPR87 predicted by Ramachandran plot and good 3-D structure compatibility as assessed by DOPE score.  Molecular dynamics (MD) simulation of models is studied of protein by conjugate gradient method. The DRY-motif (Asp- Arg-Tyr sequence) at the end of helix 3 is highlighted, where the G-protein binds and thus the activation signals are transduced. Protein-ligand interactions shows highest dock score with doxorubicin is 96.654, and involved binding site residues of GPR87 are Phe67, Lys247, Lys249, Asn330 and Asp357. In search for a better inhibitor for GPR87, insilico modification of some anti-cancer ligands shows doxorubicin has shown the highest binding affinity with GPR87. So our study provides an early insight into the structure of major drug target GPR87, thus facilitating the inhibitor design.