title: Antiviral drug acyclovir exhibits antitumor activity via targeting βTrCP1: Molecular docking and dynamics simulation study.
abstract: The critical role of βTrCP1 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 βTrCP1-WD40 domain with ACV and its phospho-derivatives (ACVMP, ACVDP and ACVTP). Consequently, through principal component analysis, βTrCP1-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 βTrCP1-WD40 specific β-propeller. The outcomes of this study may provide a platform for rational design of specific and potent inhibitor against βTrCP1, with special emphasis on anticancer activity.
authors.affiliation: National Centre for Bioinformatics, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
authors.forename: Shagufta
authors.initials: S
authors.lastname: Shafique
authors.affiliation: National Centre for Bioinformatics, Quaid-i-Azam University, Islamabad, 45320, Pakistan. Electronic address: sajidrwp@yahoo.co.uk.
authors.forename: Sajid
authors.initials: S
authors.lastname: Rashid
mesh_terms: D000212:Acyclovir / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D001059:Apoproteins / Q000737:chemistry; D001665:Binding Sites; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D025341:Principal Component Analysis; D017433:Protein Structure, Secondary; D013816:Thermodynamics; D013997:Time Factors; D044844:beta-Transducin Repeat-Containing Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D001059:Apoproteins; D044844:beta-Transducin Repeat-Containing Proteins; D000212:Acyclovir
keywords: ACV; Molecular docking; Molecular dynamics simulation; βTrCP1