title: Diffusional channeling in the sulfate-activating complex: combined continuum modeling and coarse-grained brownian dynamics studies.
abstract: Enzymes required for sulfur metabolism have been suggested to gain efficiency by restricted diffusion (i.e., channeling) of an intermediate APS(2-) between active sites. This article describes modeling of the whole channeling process by numerical solution of the Smoluchowski diffusion equation, as well as by coarse-grained Brownian dynamics. The results suggest that electrostatics plays an essential role in the APS(2-) channeling. Furthermore, with coarse-grained Brownian dynamics, the substrate channeling process has been studied with reactions in multiple active sites. Our simulations provide a bridge for numerical modeling with Brownian dynamics to simulate the complicated reaction and diffusion and raise important questions relating to the electrostatically mediated substrate channeling in vitro, in situ, and in vivo.
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California, USA. ycheng@mcammon.ucsd.edu
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Cheng
authors.forename: Chia-En A
authors.initials: CE
authors.lastname: Chang
authors.forename: Zeyun
authors.initials: Z
authors.lastname: Yu
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Zhang
authors.forename: Meihao
authors.initials: M
authors.lastname: Sun
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Leyh
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Holst
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D003198:Computer Simulation; D004789:Enzyme Activation; D015640:Ion Channel Gating; D008956:Models, Chemical; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013431:Sulfates / Q000737:chemistry* / Q000378:metabolism
chemical_list: D013431:Sulfates; D000255:Adenosine Triphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C019617:adenylylsulfate kinase