Taxifolin inhibits GTP binding in wild Apo and mutant (V12G) Apo forms of Ras: Molecular docking and molecular dynamics simulation study


Abstract

Ras proteins, the inner plasma membrane localized small G proteins, are involved in the transduction of external stimuli to its main effector Raf kinase. Point mutation in the H-Ras p21 (G12V) leads to loss of intrinsic GTPase activity so that Ras-GTP complex continuously relay signal which is associated with human cancers. Activation of oncogenic receptor tyrosine kinases also a prominent cause of continuous signal transduction through wild Ras. Taxifolin, a plant originated polyphenol, is a principal active component of several plants such as Larix gmelini. Molecular docking revealed that taxifolin captured GTP binding site in apo Ras (wild/mutant). This interaction might be valuable to target newly synthesized nucleotide unbound Ras. Molecular dynamic simulation revealed that binding of taxifolin was stable at GTP binding site of different Ras forms and may lead to improper functioning of Ras in cancer cells for cancer chemotherapeutics.



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