molecular dynamics simulations reveal proton transfer pathways in cytochrome c-dependent nitric oxide reductase分子动力学模拟显示质子转移通路在细胞色素c-dependent一氧化氮还原酶.pdfVIP

Molecular Dynamics Simulations Reveal Proton Transfer Pathways in Cytochrome C-Dependent Nitric Oxide Reductase 1 2¤ 2 1,3,4 Andrei V. Pisliakov *, Tomoya Hino , Yoshitsugu Shiro , Yuji Sugita 1Theoretical Molecular Science Laboratory, RIKEN Advanced Science Institute, Wako-shi, Saitama, Japan, 2 RIKEN SPring-8 Center, Sayo, Hyogo, Japan, 3 Computational Biophysics Research Team, RIKEN Advanced Institute for Computational Science, Chuo-ku, Kobe, Japan, 4 Laboratory for Biomolecular Function Simulation, RIKEN Quantitative Biology Center, Chuo-ku, Kobe, Japan Abstract Nitric oxide reductases (NORs) are membrane proteins that catalyze the reduction of nitric oxide (NO) to nitrous oxide (N O), 2 which is a critical step of the nitrate respiration process in denitrifying bacteria. Using the recently determined first crystal structure of the cytochrome c-dependent NOR (cNOR) [Hino T, Matsumoto Y, Nagano S, Sugimoto H, Fukumori Y, et al. (2010) Structural basis of biological N2O generation by bacterial nitric oxide reductase. Science 330: 1666–70.], we performed extensive all-atom molecular dynamics (MD) simulations of cNOR within an explicit membrane/solvent environment to fully characterize water distribution and dynamics as well as hydrogen-bonded networks inside the protein, yielding the atomic details of functionally important proton channels. Simulations reveal two possible proton transfer pathways leading from the periplasm to the active site, while no pathways from the cytoplasmic side were found, consistently