title: Releasing of the chromophore from the drug delivery protein C-1027: a molecular dynamics simulations study.
abstract: The aromatized chromophore (Chr) of C-1027 with selective DNA-cleaving ability, which is stabilized and delivered by the apoprotein (Apo) in vitro, is not released until the holoprotein (Apo+Chr) penetrates into the cultured cancer cells. As a drug delivery system, the holoprotein has gained much attention in clinical application. However, the Chr-releasing mechanism is ambiguous so far. In this paper, the releasing pathway is investigated using conventional molecular dynamics (MD), essential dynamics (ED), essential dynamics sampling and steered molecular dynamics (SMD) simulations. The results indicate that the releasing paths are related to the local motions of three loops: L3 (Val39-Gln42), L7 (Thr75-Thr79) and L9 (Asn97-Leu100). The major obstacles to Chr releasing come from steric hindrance, direct hydrogen bonds and hydrophobic interactions formed by the three loops, and Ser98 is an important residue in the releasing process. The most favorable direction of releasing is almost parallel to the connection between L7 and L3. Releasing from the direction, Chr only needs to break three hydrogen bonds from Ser98 and Pro76 and the weakest steric hindrance.
authors: State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun, 130023, People's Republic of China.
authors: Yi-bo
authors: YB
authors: Wang
authors: Xi
authors: X
authors: Zhao
authors: Hui
authors: H
authors: Yu
authors: Xu-ri
authors: XR
authors: Huang
mesh_terms: D000617:Aminoglycosides / Q000737:chemistry*; D001059:Apoproteins / Q000737:chemistry; D053281:Enediynes / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation
chemical_list: D000617:Aminoglycosides; D001059:Apoproteins; D053281:Enediynes; C058024:C 1027