Poster Presenter

Molecular Dynamics Simulations Investigation of Neocarzinostatin Chromophore Releasing Pathways from the Holo-NCS Protein
Xi Zhao, Song Wang, Xue-feng Gao, Xu-ri Huang, Chia-chung Sun

The enediyne ring chromophore with strong DNA cleavage activity of neocarzinostatin is labile and therefore stabilization by forming the complex (carrying protein + chromophore: holo-NCS). Though holo-NCS has gained much attention in clinical use as well as for drug delivery systems, the chromophore-releasing mechanism to trigger binding to the target DNA with high affinity and producing DNA damage remain unclear. Three possible pathways were identified by conventional MD, essential dynamics and essential dynamics sampling. One of the paths runs along the naphthoate moiety; the other runs along the amino sugar moiety; the third along the enediyne ring. Further, calculated forces and time by FPMD (force-probe molecular dynamics) suggest that the opening of the naphthoate moiety is most favorable pathway. In addition, conformational analyses indicated that the chromophore release is only local motions for the protein.