Ankur Chaudhuri and Sibani Chakraborty
West Bengal State University, Department of Microbiology, Barasat, P.O.- Berunanpukuria, Malikapur, North 24Pgns, Kolkata 700126, West Bengal, India
Bone morphogenic protein1 (BMP1), a small subgroup of the astacin family are important drugable targets as it is responsible for a number of diseases ranging from keloids, to formation of surgical adhesions, to deep-seated fibroses of organs. In this study a ligand based pharmacophore approach has been used for the selection of potentially active compounds which will help to understand the inhibitory activities of BMP1 further by molecular modeling and dynamics simulation methods. In this ligand-based pharmacophore study, we used the 3D structure of BMP1 (PDB ID: 3EDG) as target against a ligand dataset of 50 compounds for in silico analysis. Using this dataset of known inhibitors, a pharmacophore model was selected on the basis of a highest correlation coefficient (R), lowest total cost and root mean square deviation (rmsd) values. The pharmacophore model of the candidate inhibitors comprised four features, including two hydrogen bond acceptor and two hydrophobic. This model was then used for virtual screening of compounds taken from Maybridge/Chembridge databases. The selective hit compounds were docked to the crystal structure of BMP1 to further filter these hits. We suggest that the new hits reported in our study may help in the design of potent inhibitors against BMP1.