Combined virtual screening, MMPBSA, molecular docking and dynamics studies against deadly anthrax: An in silico effort to inhibit Bacillus anthracis nucleoside hydrolase

摘要

Abstract Anthrax is a deadly disease caused by Bacillus anthracis , a dangerous biological warfare agent employed for both military and terrorist purposes. A critical selective target for chemotherapy against this disease is nucleoside hydrolase (NH), an enzyme still not found in mammals. In the current study, we have performed molecular docking and dynamics studies, aiming to propose the new potent inhibitors of B. anthracis NH among National Cancer Institute (NCI) Diversity Set. We also analyzed the principal interactions of proposed compounds with the active site residues of NH and the relevant factors to biological activity. Additionally, the physic-chemical properties of free and inhibitor bound NH were evaluated and discussed. Our data showed that compound NSC79887 is a good candidate to inhibit NH and also for biological tests and further development. Also, ADMET prediction revealed that all physic-chemical parameters are within the acceptable range defined for human use. Highlights ? The new potent inhibitor against Bacillus anthracis nucleoside hydrolase is introduced by virtual screening. ? The inhibition mechanism and physico-chemical properties of free and inhibitor-bond NH were evaluated by MD simulations. ? ADMET analysis data showed that compound NSC7988 could be a potential inhibitor of therapeutic targets of deadly anthrax. ]]>