@article {787, title = {On the Origin of Proton Mobility Suppression in Aqueous Solutions of Amphiphiles}, journal = {J. Phys. Chem. B }, volume = {117}, year = {2013}, pages = {15426-15435}, doi = {10.1021/jp4051726}, author = {Xu, J. and Yamashita, T. and Agmon, N. and G. A. Voth} } @article {716, title = {Infrared Spectrum of the Hydrated Proton in Water}, journal = {J. Phys. Chem. Lett.}, volume = {2}, year = {2011}, pages = {81-86}, doi = {10.1021/jz101536b}, author = {Xu, J. and Zhang, Y. and G. A. Voth} } @article {711, title = {Structure and Dynamics of Concentrated Hydrochloric Acid Solutions}, journal = {J. Phys. Chem. B}, volume = {114}, year = {2010}, pages = {9555{\textendash}9562}, doi = {10.1021/jp102516h}, author = {Xu, J. and Izvekov, S. and G. A. Voth} } @article {427, title = {Unusual Hydrophobic Interactions in Acidic Aqueous Solutions}, journal = {J. Phys. Chem. B}, volume = {113}, year = {2009}, pages = {7291-7297}, doi = {10.1021/jp9025909}, author = {Chen, H. and Xu, J. and G. A. Voth} } @article {715, title = {Redox-Coupled Proton Pumping in Cytochrome c Oxidase: Further Insights from Computer Simulation}, journal = {Biochim. et Biophys. Acta-Bioenergetics}, volume = {1777}, year = {2008}, pages = {196-201}, doi = {10.1063/1.2976663}, author = {Xu, J. and G. A. Voth} } @article {659, title = {Proton Solvation and Transport in Aqueous and Biomolecular Systems: Insights from Computer Simulations}, journal = {J Phys Chem B}, volume = {111}, number = {17}, year = {2007}, note = {Swanson, Jessica M J Maupin, C Mark Chen, Hanning Petersen, Matt K Xu, Jiancong Wu, Yujie Voth, Gregory A R01 GM053148-12/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, U.S. Gov{\textquoteright}t, Non-P.H.S. Review United States The journal of physical chemistry. B J Phys Chem B. 2007 May 3;111(17):4300-14. Epub 2007 Apr 13.}, pages = {4300-14}, abstract = {

The excess proton in aqueous media plays a pivotal role in many fundamental chemical (e.g., acid-base chemistry) and biological (e.g., bioenergetics and enzyme catalysis) processes. Understanding the hydrated proton is, therefore, crucial for chemistry, biology, and materials sciences. Although well studied for over 200 years, excess proton solvation and transport remains to this day mysterious, surprising, and perhaps even misunderstood. In this feature article, various efforts to address this problem through computer modeling and simulation will be described. Applications of computer simulations to a number of important and interesting systems will be presented, highlighting the roles of charge delocalization and Grotthuss shuttling, a phenomenon unique in many ways to the excess proton in water.

}, keywords = {Biological Transport *Computer Simulation *Protons Solubility Solvents/*chemistry Water/chemistry}, doi = {10.1021/jp070104x}, author = {Swanson, J. M. and Maupin, C. M. and Chen, H. and Petersen, M. K. and Xu, J. and Y. Wu and G. A. Voth} } @article {712, title = {Storage of an Excess Proton in the Hydrogen-bonded Network of the D-pathway of Cytochrome c Oxidase: Identification of a Protonated Water Cluster}, journal = {J Am Chem Soc}, volume = {129}, number = {10}, year = {2007}, note = {Xu, Jiancong Sharpe, Martyn A Qin, Ling Ferguson-Miller, Shelagh Voth, Gregory A GM053148/GM/NIGMS NIH HHS/United States GM26916/GM/NIGMS NIH HHS/United States R01 GM053148-05/GM/NIGMS NIH HHS/United States R01 GM053148-13/GM/NIGMS NIH HHS/United States R37 GM026916-29/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural United States Journal of the American Chemical Society J Am Chem Soc. 2007 Mar 14;129(10):2910-3. Epub 2007 Feb 20.}, pages = {2910-3}, abstract = {

The mechanism of proton transport in the D-pathway of cytochrome c oxidase (CcO) is further elucidated through examining a protonated water/hydroxyl cluster inside the channel. The second generation multi-state empirical valence bond (MS-EVB2) model was employed in a molecular dynamics study based on a high-resolution X-ray structure to simulate the interaction of the excess proton with the channel environment. Our results indicate that a hydrogen-bonded network consisting of about 5 water molecules surrounded by three side chains and two backbone groups (S197, S200, S201, F108) is involved in storage and translocation of an excess proton to the extracellular side of CcO.

}, keywords = {Computer Simulation Electron Transport Complex IV/*chemistry/metabolism Hydrogen Bonding Models, Molecular Molecular Structure *Protons Rhodobacter sphaeroides/enzymology Water/*chemistry}, doi = {10.1021/ja067360s}, url = { }, author = {Xu, J. and Sharpe, M. A. and Qin, L. and Ferguson-Miller, S. and G. A. Voth} } @article {714, title = {Free Energy Profiles for H+ Conduction in the D-pathway of Cytochrome c Oxidase: A Study of the Wild Type and N98D Mutant Enzymes}, journal = {Biochim Biophys Acta}, volume = {1757}, number = {7}, year = {2006}, note = {Xu, Jiancong Voth, Gregory A 1 S10 RR17214-01/RR/NCRR NIH HHS/United States R01 GM053148/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov{\textquoteright}t Netherlands Biochimica et biophysica acta Biochim Biophys Acta. 2006 Jul;1757(7):852-9. Epub 2006 May 24.}, pages = {852-9}, abstract = {

The molecular mechanism for proton conduction in the D-pathway of Cytochrome c Oxidase (CcO) is investigated through the free energy profile, i.e., potential of mean force (PMF) calculations of both the native enzyme and the N98D mutant. The multistate empirical valence bond (MS-EVB) model was applied to simulate the interaction of an excess proton with the channel environment. In the study of the wild type enzyme, the PMF reveals the previously proposed proton trap inside the channel; it also shows a high free energy barrier against the passage of proton at the entry of the channel, where two conserved asparagines (ASN80/98) may be essential for the gating of proton uptake. We also present data from an investigation of the N98D mutant, which has been previously shown to completely eliminate proton pumping but significantly enhance the oxidase activity in Rhodobacter sphaeroides. These results suggest that mutating Asn98 to negatively charged aspartate will create an unfavorable energy barrier sufficiently high to prevent the overall proton uptake through the D-pathway, whereas with a protonated aspartic acid the proton conduction was found to be accelerated. Plausible explanations for the origin of the uncoupling of proton pumping from the oxidase activity will be discussed.

}, keywords = {Animals Cattle Electron Transport Complex IV/genetics/*metabolism Hydrogen/*metabolism Myocardium/enzymology Point Mutation Thermodynamics}, doi = {10.1016/j.bbabio.2006.05.028}, author = {Xu, J. and G. A. Voth} } @article {713, title = {Computer Simulation of Explicit Proton Translocation in Cytochrome c Oxidase: the D-pathway}, journal = {Proc Natl Acad Sci U S A}, volume = {102}, number = {19}, year = {2005}, note = {Xu, Jiancong Voth, Gregory A R01 GM053148/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, U.S. Gov{\textquoteright}t, P.H.S. United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2005 May 10;102(19):6795-800. Epub 2005 Apr 27.}, pages = {6795-800}, abstract = {

Proton translocation in the D-pathway of cytochrome c oxidase has been studied by a combination of classical molecular dynamics and the multistate empirical valence bond methodology. This approach allows for explicit Grotthuss proton hopping between water molecules. According to mutagenesis experiments, the role of proton donor/acceptor along the D-pathway is carried by the highly conserved residue Glu-242. The present multistate empirical valence bond simulations indicate that the protonation/deprotonation state of Glu-242 is strongly coupled to the distance of proton propagation in the D-pathway. The proton was seen to travel the full length of the D-pathway when Glu-242 was deprotonated; however, it was trapped halfway along the path when Glu-242 was protonated. Further investigation in terms of both proton dynamical properties and free energy calculations for the pathway of proton transport provides evidence for a two-step proton transport mechanism in the D-pathway.

}, keywords = {Animals Biophysics/*methods Cattle Computer Simulation Crystallography, Molecular Models, Statistical Mutagenesis Protons Serine/chemistry Static Electricity Thermodynamics Time Factors Water/chemistry, X-Ray Electron Transport Complex IV/*chemistry Glutamic Acid/chemistry Mitochondria/metabolism Models}, doi = {10.1073/pnas.0408117102}, author = {Xu, J. and G. A. Voth} }