Molecular Docking, Standard Dynamics Trajectory Analysis and Density Functional Theory Studies of Potent Antibacterial Compounds Against Staphylococcus aureus AacA-AphD Protein to Identify Potential Lead Molecules

Abstract

The in silico interactions of four potent antimicrobial compounds (3c, 3r, 3a, and 3j) with the microbial protein Aminoglycoside Phosphotransferase (2'')-Ia S376N mutant) were examined through molecular docking, molecular dynamics simulation, and density functional theory (DFT). Molecular docking was performed using LibDock and CDOCKER docking programs. The predicted CDOCKER_ energy of antimicrobial compounds (3c, 3r, 3a, and 3j) was (-13.8134,-13.2361,-7.0566 and-1.4893 kcalmol-1) with microbial protein 6CH4 as the best conformer. Molecular docking outcomes significantly supported the molecular simulation data. These results indicated that the potent antimicrobial compound 3c showed a highly stable agonistic affinity for the receptor. Trajectory analysis revealed that compound 3c stably interacted with and did not cause any energy changes in the residues of the protein. In addition, density functional theory analysis strongly supported these computational studies. Compound 3c exhibits a lower HOMO–LUMO energy gap. This confirmed that it was the most active molecule among the four chosen compounds. The structural information and in silico observations obtained from the study could aid in screening and fabricating new promising antimicrobial analogs for the treatment of microbial infections.