186 Molecular dynamics and ligand based studies for the validation of potential inhibitors for SrtA against Bacillus anthracis

Abstract

SrtA enzymes cleave the sorting signals of secreted proteins to form isopeptide (amide) bonds between the secreted proteins and peptidoglycan or polypeptides to function as the principal architects of the Bacillus anthracis. Inhibition of SrtA can completely eradicate the growth of B. anthracis due to the lack of signals and so the SrtA is universally accepted as the drug target for all gram positive pathogens. Here, with the reported compounds, the pharmacophore-based virtual screening protocol has been used to obtain similar pharmacological property that derived new compounds to inhibit the SrtA structure. New compounds on AAAHR Pharmacophore hypothesis screening were treated with four phase of docking protocols with combined Glide-QPLD docking approach and charge accuracy variations were dominated by QM/MM approach. Finally, the compounds of 19941, 14704, 121962, 20137, and 19533 from binding db, Chembridge db, and Toslab were succeeded from the screening; these compounds are having better scoring, energy parameters, ADME physio/chemical properties, tendency to transfer the electrons between the protein–ligand interactions, and these compounds also predict having cell adhesion inhibitory activity. These screened compounds have better stability at active site loop regions with strong bonding interactions and these compounds on clinical trials will definitely emerge as better SrtA inhibitor against the B. anthracis .