Albany 2013: Book of Abstracts
June 11-15 2013
©Adenine Press (2012)
Molecular Dynamics and Ligand based studies for the validation of potential inhibitors for SrtA against Bacillus anthracis
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 B.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 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 predicted for 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.
Figure: AAAHR pharmacophore model hypothesis obtained from the known SrtA inhibitors.
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Sanjeev Kumar Singh
Computer Aided Drug Design and Molecular Modeling Lab