MOLECULAR DOCKING STUDIES OF SOME TETRAHYDRONAPHTALENE-BENZIMIDAZOLE DERIVATIVES AND CORRELATION WITH THEIR CORRESPONDING ANTI-MRSA ACTIVITIES

Objective: Methicillin- resistant S. aureus (MRSA) is a type of bacteria which is resistant to various types of antibiotics and causes mortality in hospital environment and community. To further investigate the inhibition activity of previously synthesized retinoidal compounds against MRSA, docking studies of these compounds with MRSA pyruvate kinase (PK) were made. Material and Method: As a first step, ligand preparation procedure has been made. For optimization of compounds, Hyperchem Professional was used. Molecular Mechanics Force Field (MMFF) and semi-empirical methods have been implemented in this program. After converting the ligands to pdb files, charges and torsions were added via AutoDockTools 1.5.6. Macromolecule file for MRSA Pyruvate kinase (PDB ID:3T07) was procured from protein data bank. Appropriate chain for binding was chosen via UCSF Chimera. Polar hydrogens and Gasteiger charges were added to macromolecule via AutoDockTools 1.5.6. Gridbox has been predicted by protein- ligand complex which is currently present in protein data bank and prepared via same software. Docking process was made via AutoDock Vina. For MIC values of retinoidal compounds, previous study by Ates-Alagoz et al. has been used. In addition, some QSAR properties were calculated via Hyperchem Professional and were also interpreted. Result and Discussion: Compounds 1, 4, 5, 6, 7 were selected for their PK inhibitor activities. Addition to their relatively lower MIC values, they also show similar binding modes to previously presented PK inhibitor candidates. Binding of compounds with His365 and Ile361 in both monomeric units of PK, creates a bridge that links these units. In terms of QSAR, molecular volume below 1010 ？3 is favorable. Moreover, log P does not have an impact on activity. This binding mode and interactions with aminoacid residues may be the cause of their promising inhibition activity against MRSA Pyruvate kinase