Abstract

Background: Docking and 3D QSAR studies were performed on Inhibitor of Bacterial DNA gyrase to develop a predictive Common Pharmacophore Hypothesis (CPH). Molecular interaction and binding affinities of these analogues, differing with nucleotides and amino acids are studied are performed.

Methods: Biological activity is predicted by QSAR approach by relating the set of compounds. QSAR study was applied using PHASE, the docking studies were performed using Glide module and Prime/MM-GB/SA is used for free energy ligand binding calculations.

Results: We obtained high pred_r2 value (pred_r2= 0. 9239), suggesting a significant external predictive ability of the QSAR model. Mutant docking score is -9. 023. In Wild type docking it shows lower binding energy and binding affinity is a decrease so, docking score of wild most dock 26 molecule is - 6.093. Protein shows various sites for molecular interaction, so from MM-GBSA.

Conclusion: In the present study, development of predictive hypothesis (CPH) for 4-substituted cyclobutylphenyl quinoline derivatives and CPH were generated and results were interpreted on a developed model containing five features gives good and predictive statistical significance. Docking studies explained hydrogen bonding, pi-pi stacking with deoxy-ribonucleotide and with Ala 1120 and positive charge with deoxyribonucleotide. MM-GBSA explains the binding affinity of most docked ligand with protein.

Keywords: 3D-QSAR, PHASE, Docking, CPH, 2XCS, DG, DC.

Graphical Abstract