Molecular dynamics simulations for understanding dual ubiquitination mechanisms to consider S-phase kinase-associated protein 2 (SKP2) as a potential drug target in breast cancer

IntroductionDual ubiquitination mediated by S-phase kinase-associated protein 2 (SKP2) plays a critical role in breast cancer progression by directing substrates toward either proteasomal degradation or signaling activation. However, the structural determinants governing SKP2 recognition of different ubiquitin-linked substrates, particularly p27 and Akt1, remain poorly understood.MethodsTo investigate this mechanism, integrative computational approaches including protein–protein docking, molecul