The enediyne ring chromophore with strong DNA cleavage activity of neocarzinostatin is labile and therefore must be stabilized by forming the complex (binding 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 remains unclear. In this work, the complex of neocarzinostatin and binding protein corresponding to the complex have been studied, and the mechanism of the chromophore-releasing from binding protein is studied with molecular simulation and steered molecular dynamics, too. Further, calculated forces and time by FPMD (force-probe molecular dynamics) suggest that the opening of the naphthoate moiety should be the most favorable pathway.

Key words: neocarzinostatin, enediyne ring chromophore, molecular dynamics simulation