Screening of Bioactive Compounds against Nonreceptor Fyn Kinase: Virtual Screening and Network Approach

Sudharsana sundarrajan, Thabitha Amalraj, Sweta Kumari, Sajitha Lulu, Mohanapriya Arumugam

Abstract


Tyrosine phosphorylation is a key controlling mechanism in signal transduction and enzyme activity regulation. Dysfunction of Fyn kinase, a unique member of non-receptor Src kinase family is implicated in oncogenesis, T-cell mediated diseases and neuronal disorders. Fyn kinase has been recognized as an important target for anti-cancer therapeutics. An insilico virtual screening of open and closed states of Fyn with seventy phytochemicals used in cancer treatment was carried out.  Molecular properties and bioactive spectrum analysis further improved the screening process by forming a data set containing seven potential hits. Ligand efficiency score which combines biological and chemical space together identified three secondary metabolites apigenin, genistein and quercetin as efficient inhibitors of Fyn kinase.  A reverse virtual screening approach validated the target selection by identifying Src kinase family members as potential drug targets. Drug-target interaction network based on feature scores of 22 phytochemicals which survived the initial screening process further validated our findings.  A conceptual optimization may be required to reduce attrition and increase the activity of the lead.

Keywords


Fyn kinases Src kinase Oncogenesis Ligand efficiency Reverse virtual screening Feature score Drug-target network

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References


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