TI - Insights into unbinding mechanisms upon two mutations investigated by molecular dynamics study of GSK3beta-axin complex : role of packing hydrophobic residues . AB - Glycogen synthase kinase 3beta ( GSK 3beta ) is a key component of several cellular processes including Wnt and insulin signalling pathways . The interaction of GSK3beta with scaffolding peptide axin is thought to be responsible for the effective phosphorylation of beta-catenin , the core effector of Wnt signaling , which has been linked with the occurrence of colon cancer and melanoma . It has been demonstrated that the binding of axin to GSK3beta is abolished by the single-point mutation of Val267 to Gly ( V267G ) in GSK3beta or Leu392 to Pro ( L392P ) in axin . Molecular dynamics ( MD ) simulations were performed on wild type ( WT ) , V267G mutant and L392P one to elucidate the two unbinding mechanisms that occur through different pathways . Besides , rough energy and residue -based energy decomposition were calculated by MM GBSA approach to illuminate the instability of the two mutants . The MD simulations of the two mutants and WT reveal that the structure of GSK3beta remains unchanged , while axin moves away from the interfacial hydrophobic pockets in both two mutants . Axin exhibits positional shift in V267G mutant , whereas , losing the hydrogen bonds that are indispensable for stabilizing the helix structure of wild type axin , the helix of axin is distorted in L392P mutant . To conclude , both two mutants destroy the hydrophobic interaction that is essential to the stability of GSK3beta-axin complex .