@article {795, title = {Application of the SCC-DFTB Method to Hydroxide Water Clusters and Aqueous Hydroxide Solutions}, journal = {J. Phys. Chem. B }, volume = {117}, year = {2013}, pages = {5165-5179}, doi = {10.1021/jp400953a}, author = {T. H. Choi and R. Liang and Maupin, C. M. and G. A. Voth} } @article {567, title = {Chemical Rescue of Enzymes: Proton Transfer in Mutants of Human Carbonic Anhydrase II}, journal = {J. Am. Chem. Soc.}, volume = {133}, year = {2011}, pages = {6223{\textendash}6234}, doi = {10.1021/ja1097594}, author = {Maupin, C. M. and Castillo, N. and Taraphder, S. and C. Tu, R. McKenna and Silverman, D. N. and G. A. Voth} } @article {513, title = {Defining Condensed Phase Reactive Force Fields From Ab Initio Molecular Dynamics Simulations: The Case of the Hydrated Excess Proton}, journal = {J. Chem. Theor. Comp.}, volume = {6}, year = {2010}, pages = {3223{\textendash}3232}, doi = {10.1021/ct1004438}, author = {Knight, C. and Maupin, C. M. and Izvekov, S. and G. A. Voth} } @article {568, title = {Proton Transport in Carbonic Anhydrase: Insights from Molecular Simulation}, journal = {Biochim. et Biophys. Acta - Proteins and Proteomics}, volume = {1804}, year = {2010}, pages = {332-341}, doi = {10.1016/j.bbapap.2009.09.006}, author = {Maupin, C. M. and G. A. Voth, {\textquotedblleft}, 1804, (2010).} } @article {566, title = {The Self-Consistent Charge Density Functional Tight Binding Method Applied to Liquid Water and the Hydrated Excess Proton: Benchmark Simulations}, journal = {J. Phys. Chem. B}, volume = {114}, year = {2010}, pages = {6922-6931}, doi = {10.1021/jp1010555}, author = {Maupin, C. M. and Aradi, B. and G. A. Voth} } @article {573, title = {Effect of Active-site Mutations at Asn67 on the Proton Transfer Mechanism of Human Carbonic Anhydrase II}, journal = {Biochem.}, volume = {48}, year = {2009}, pages = {7996-8005}, doi = {10.1021/bi901037u}, author = {Maupin, C. M. and Zheng, J. and Tu, C. and McKenna, R. and Silverman, D. N. and G. A. Voth} } @article {569, title = {Elucidation of the Proton Transport Mechanism in Human Carbonic Anhydrase II}, journal = {J. Am. Chem. Soc.}, volume = {131}, year = {2009}, pages = {7598-7608}, doi = {10.1021/ja8091938}, author = {Maupin, C. M. and McKenna, R. and Silverman, D. N. and G. A. Voth} } @article {570, title = {Origins of Enhanced Proton Transport in the Y7F Mutant of Human Carbonic Anhydrase II}, journal = {J. Am. Chem. Soc.}, volume = {130}, year = {2008}, pages = {11399{\textendash}11408}, doi = {10.1021/ja802264j}, author = {Maupin, C. M. and Saunders, M. G. and Thorpe, I. F. and McKenna, R. and Silverman, D. N. and G. A. Voth} } @article {446, title = {Atomic Crystal and Molecular Dynamics Simulation Structures of Human Carbonic Anhydrase II: Insights into the Proton Transfer Mechanism}, journal = {Biochemistry}, volume = {46}, number = {11}, year = {2007}, note = {Fisher, S Zoe Maupin, C Mark Budayova-Spano, Monika Govindasamy, Lakshmanan Tu, Chingkuang Agbandje-McKenna, Mavis Silverman, David N Voth, Gregory A McKenna, Robert GM25154/GM/NIGMS NIH HHS/United States GM53148/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov{\textquoteright}t United States Biochemistry Biochemistry. 2007 Mar 20;46(11):2930-7. Epub 2007 Feb 24.}, pages = {2930-7}, abstract = {

Human carbonic anhydrase II (HCA II) is a zinc-metalloenzyme that catalyzes the reversible interconversion of CO2 and HCO3-. The rate-limiting step of this catalysis is the transfer of a proton between the Zn-bound solvent molecule and residue His64. In order to fully characterize the active site structural features implicated in the proton transfer mechanism, the refined X-ray crystal structure of uncomplexed wild type HCA II to 1.05 A resolution with an Rcryst value of 12.0\% and an Rfree value of 15.1\% has been elucidated. This structure provides strong clues as to the pathway of the intramolecular proton transfer between the Zn-bound solvent and His64. The structure emphasizes the role of the solvent network, the unique positioning of solvent molecule W2, and the significance of the dual conformation of His64 in the active site. The structure is compared with molecular dynamics (MD) simulation calculations of the Zn-bound hydroxyl/His64+ (charged) and the Zn-bound water/His64 (uncharged) HCA II states. A comparison of the crystallographic anisotropic atomic thermal parameters and MD simulation root-mean-square fluctuation values show excellent agreement in the atomic motion observed between the two methods. It is also interesting that the observed active site solvent positions in the crystal structure are also the most probable positions of the solvent during the MD simulations. On the basis of the comparative study of the MD simulation results, the HCA II crystal structure observed is most likely in the Zn-bound water/His64 state. This conclusion is based on the following observations: His64 is mainly (80\%) orientated in an inward conformation; electron density omit maps infer that His64 is not charged in an either inward or outward conformation; and the Zn-bound solvent is most likely a water molecule.

}, keywords = {Amino Acid Sequence Carbonic Anhydrase II/*chemistry Computational Biology Computer Simulation Crystallization Crystallography, Molecular *Protons, X-Ray Histidine/chemistry Humans Models}, doi = {10.1021/bi062066y}, author = {Fisher, S. Z. and Maupin, C. M. and Budayova-Spano, M. and Govindasamy, L. and Tu, C. and Agbandje-McKenna, M. and Silverman, D. N. and G. A. Voth and McKenna, R.} } @article {571, title = {Preferred Orientations of His-64 in Human Carbonic Anhydrase II}, journal = {Biochemistry}, volume = {46}, number = {11}, year = {2007}, note = {Maupin, C Mark Voth, Gregory A 1 S10 RR17214-01/RR/NCRR NIH HHS/United States GM53148/GM/NIGMS NIH HHS/United States R01 GM053148-13/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural United States Biochemistry Biochemistry. 2007 Mar 20;46(11):2938-47. Epub 2007 Feb 24.}, pages = {2938-47}, abstract = {

Histidine at position 64 (His64) in human carbonic anhydrase II (HCA II) is believed to be the proton acceptor in the hydration direction and the proton donor in the dehydration direction for the rate-limiting proton transfer (PT) event. Although the biochemical effect of histidine at position 64 has been thoroughly investigated, the role of its orientation in the PT event is a topic of considerable debate. X-ray data of HCA II suggests that His64 can adopt either an "in" or "out" orientation. The "in" orientation is believed to be favored for the hydration direction PT event because the Ndelta of His64 is closer to the catalytic zinc. This orientation allows for smaller water bridges, which are postulated to be more conducive to PT. In the present work, classical molecular dynamics simulations have been conducted to elucidate the role that the His64 orientation may play in its ability to act as a proton donor/acceptor in HCA II. The free energy profile for the orientation of His64 suggests that the histidine will adopt an "in" orientation in the hydration direction, which brings Ndelta in close proximity to the catalytic zinc. When the histidine becomes protonated, it then rotates to an "out" orientation, creating a more favorable solvation environment for the protonated His64. In this "out" orientation, the imidazole ring releases the delta nitrogen{\textquoteright}s excess proton into the bulk environment. After the second PT event and when the zinc-bound water is regenerated, the His64 is again favored to reorient to the "in" orientation, completing the catalytic cycle.

}, keywords = {Amino Acid Sequence Binding Sites Carbonic Anhydrase II/*chemistry Computational Biology Computer Simulation Histidine/*chemistry Humans Models, Molecular *Molecular Conformation Thermodynamics}, doi = {10.1021/bi062170f}, author = {Maupin, C. M. 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 {572, title = {A Multistate Empirical Valence Bond Description of Protonatable Amino Acids}, journal = {J Phys Chem A}, volume = {110}, number = {2}, year = {2006}, note = {Maupin, C Mark Wong, Kim F Soudackov, Alexander V Kim, Sun Voth, Gregory A 1 S10 RR17214-01/RR/NCRR NIH HHS/United States 2R01GM53148/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural United States The journal of physical chemistry. A J Phys Chem A. 2006 Jan 19;110(2):631-9.}, pages = {631-9}, abstract = {

The multistate empirical valence bond (MS-EVB) model, which was developed for molecular dynamics simulations of proton transport in water and biomolecular systems, is extended for the modeling of protonatable amino acid residues in aqueous environments, specifically histidine and glutamic acid. The parameters of the MS-EVB force field are first determined to reproduce the geometries and energetics of the gas phase amino acid-water clusters. These parameters are then optimized to reproduce experimental pK(a) values. The free energy profiles for acid ionization and the corresponding pK(a) values are calculated by MS-EVB molecular dynamics simulations utilizing the umbrella sampling technique, with the center of excess charge coordinate chosen as the dissociation reaction coordinate. A general procedure for fitting the MS-EVB parameters is formulated, which allows for the parametrization of other amino acid residues with protonatable groups and the subsequent use of the MS-EVB approach for molecular dynamics simulations of proton transfer processes in proteins involving protonation/deprotonation of the protonatable amino acid groups.

}, keywords = {Amino Acids/*chemistry Electrons *Models, Molecular Proteins/chemistry *Protons}, doi = {10.1021/jp053596r}, author = {Maupin, C. M. and Wong, K. F. and Soudackov, A. V. and Kim, S. and G. A. Voth} }