MOLECULAR SIMULATIONS OF NEOCARZINOSTATIN CHROMOPHORE RELEASE MECHANISM

Neocarzinostatin (NCS) is an antitumor chromophore carrier protein with many applications in clinical use such as drug delivery system; however, so far its chromophore-releasing mechanism remains unclear. In this contribution the process and pathway of the chromophore releasing from holoprotein are revealed by conventional molecular dynamics simulations and essential dynamics (ED) sampling method. The results are consistent with the model for ligand release proposed in [D. H. Chin et al., J Biol Chem 281: 16025, 2006]. The further analysis suggests that the conformational changes of loop 99-104 and motions of side-chain of residue Phe78 are important factors for chromophore release; the opening state of loop 99-104 is a precondition for the release of ligand.