Antiviral drug acyclovir exhibits antitumor activity via targeting ßTrCP1: Molecular docking and dynamics simulation study.

ABSTRACT

The critical role of ßTrCP1 in cancer development makes it a discerning target for the development of small drug like molecules. Currently, no inhibitor exists that is able to target its substrate binding site. Through molecular docking and dynamics simulation assays, we explored the comparative binding pattern of ßTrCP1-WD40 domain with ACV and its phospho-derivatives (ACVMP, ACVDP and ACVTP). Consequently, through principal component analysis, ßTrCP1-ACVTP was found to be more stable complex by obscuring a reduced conformational space than other systems. Thus based on the residual contribution and hydrogen bonding pattern, ACVTP was considered as a noteworthy inhibitor which demarcated binding in the cleft formed by ßTrCP1-WD40 specific ß-propeller. The outcomes of this study may provide a platform for rational design of specific and potent inhibitor against ßTrCP1, with special emphasis on anticancer activity.