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See detailHydrogen-Bonded Networks Along and Bifurcation of the E-Pathway in Quinol:Fumarate Reductase
Herzog, Elena; Gu, Wei UL; Juhnke, Hanno D. et al

in Biophysical Journal (2012), 103(6), 1305-1314

The E-pathway of transmembrane proton transfer has been demonstrated previously to be essential for catalysis by the diheme-containing quinol:fumarate reductase (QFR) of Wolinella succinogenes. Two ... [more ▼]

The E-pathway of transmembrane proton transfer has been demonstrated previously to be essential for catalysis by the diheme-containing quinol:fumarate reductase (QFR) of Wolinella succinogenes. Two constituents of this pathway, Glu-C180 and heme bp ring C (b(D)-C-) propionate, have been validated experimentally. Here, we identify further constituents of the E-pathway by analysis of molecular dynamics simulations. The redox state of heme groups has a crucial effect on the connectivity patterns of mobile internal water molecules that can transiently support proton transfer from the b(D)-C-propionate to Glu-C180. The short H-bonding paths formed in the reduced states can lead to high proton conduction rates and thus provide a plausible explanation for the required opening of the E-pathway in reduced QFR. We found evidence that the b(D)-C-propionate group is the previously postulated branching point connecting proton transfer to the E-pathway from the quinol-oxidation site via interactions with the heme bp ligand His-C44. An essential functional role of His-C44 is supported experimentally by site-directed mutagenesis resulting in its replacement with Glu. Although the H44E variant enzyme retains both heme groups, it is unable to catalyze quinol oxidation. All results obtained are relevant to the QFR enzymes from the human pathogens Campylobacter jejuni and Helicobacter pylori. [less ▲]

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See detailDesign of a Gated Molecular Proton Channel
Gu, Wei UL; Zhou, Bo; Geyer, Tihamer et al

in Angewandte Chemie International Edition (2011), 50(3), 768-771

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See detailAdhesive water networks facilitate binding of protein interfaces
Ahmad, Mazen; Gu, Wei UL; Geyer, Tihamer et al

in Nature Communications (2011), 2

Water structure has an essential role in biological assembly. Hydrophobic dewetting has been documented as a general mechanism for the assembly of hydrophobic surfaces; however, the association mechanism ... [more ▼]

Water structure has an essential role in biological assembly. Hydrophobic dewetting has been documented as a general mechanism for the assembly of hydrophobic surfaces; however, the association mechanism of hydrophilic interfaces remains mysterious and cannot be explained by simple continuum water models that ignore the solvent structure. Here we study the association of two hydrophilic proteins using unbiased extensive molecular dynamics simulations that reproducibly recovered the native bound complex. The water in the interfacial gap forms an adhesive hydrogen-bond network between the interfaces stabilizing early intermediates before native contacts are formed. Furthermore, the interfacial gap solvent showed a reduced dielectric shielding up to distances of few nanometres during the diffusive phase. The interfacial gap solvent generates an anisotropic dielectric shielding with a strongly preferred directionality for the electrostatic interactions along the association direction. [less ▲]

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See detailAtomistic Simulation of Water Percolation and Proton Hopping in Nation Fuel Cell Membrane
Devanathan, Ram; Venkatnathan, Arun; Rousseau, Roger et al

in Journal of Physical Chemistry B (2010), 114(43), 13681-13690

We have performed a detailed analysis of water clustering and percolation in hydrated Nafion configurations generated by classical molecular dynamics simulations. Our results show that at low hydration ... [more ▼]

We have performed a detailed analysis of water clustering and percolation in hydrated Nafion configurations generated by classical molecular dynamics simulations. Our results show that at low hydration levels H(2)O molecules are isolated and a continuous hydrogen-bonded network forms as the hydration level is increased. Our quantitative analysis has established a hydration level (lambda) between 5 and 6 H(2)O/SO(3)(-) as the percolation threshold of Nation. We have also examined the effect of such a network on proton transport by studying the structural diffusion of protons using the quantum hopping molecular dynamics method. The mean residence time of the proton on a water molecule decreases by 2 orders of magnitude when the lambda value is increased from 5 to 15. The proton diffusion coefficient in Nation at a lambda value of 15 is about 1.1 x 10(-5) cm(2)/s in agreement with experiment. The results provide quantitative atomic-level evidence of water network percolation in Nafion and its effect on proton conductivity. [less ▲]

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See detailDownhill Binding Energy Surface of the Barnase-Barstar Complex
Wang, Ling; Siu, Shirley W. I.; Gu, Wei UL et al

in Biopolymers (2010), 93(11), 977-985

We have employed biased molecular dynamics simulations in explicit solvent to characterize the one-dimensional potential of mean force for the dissociation process of the barnase-barstar protein-protein ... [more ▼]

We have employed biased molecular dynamics simulations in explicit solvent to characterize the one-dimensional potential of mean force for the dissociation process of the barnase-barstar protein-protein complex. Unbinding of barstar from wild-type barnase was compared with dissociation from four charge-deletion mutants of barnase. Interestingly, we find in all cases that unbinding of barnase and barstar is an uphill process on a smooth, tilted energy landscape. The total free energy difference between the dissociated and bound state was similar for wild-type barnase-barstar and for the R87A mutant of barnase. The values for the three other mutant barnase mutants K27A, R59A, and R83Q were only about half as much. Besides, we have analyzed the conformational dynamics of important residues at the barnase-barstar interface. In the bound state, their conformational fluctuations are reduced relatively to the free state because of the formation of intermolecular contacts. Interestingly, we find that some residues also show decreased mobility at intermediate stages of the unbinding process suggesting that these residues may be involved in the first contacts being formed on binding. (C) 2010 Wiley Periodicals, Inc. Biopolymers 93: 977-985, 2010. [less ▲]

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See detailTightly Connected Water Wires Facilitate Fast Proton Uptake at The Proton Entrance of Proton Pumping Proteins
Gu, Wei UL; Helms, Volkhard

in Journal of the American Chemical Society (2009), 131(6), 2080-

Tightly connected water wires (TCW) exist in systems with nonconfined water like the solvated membrane proton pump system. The TCWs that connect to the negatively charged proton entrance facilitate the ... [more ▼]

Tightly connected water wires (TCW) exist in systems with nonconfined water like the solvated membrane proton pump system. The TCWs that connect to the negatively charged proton entrance facilitate the fast proton uptake of the proton pump. They function as a direct proton bridge or/and stabilizer of protons within the Coulomb cage of the proton entrance. Negatively charged residue(s) at the proton entrance induce a large population of long TCWs. Additional negatively charged residues increase the population of such long TCWs and, thus, raise the possibility to capture proton from the solution. [less ▲]

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See detailMechanism of fast peptide recognition by SH3 domains
Ahmad, Mazen; Gu, Wei UL; Helms, Volkhard

in Angewandte Chemie International Edition (2008), 47(40), 7626-7630

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See detailDynamic protonation equilibrium of solvated acetic acid
Gu, Wei UL; Frigato, Tomaso; Straatsma, Tjerk P. et al

in Angewandte Chemie International Edition (2007), 46(16), 2939-2943

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See detailDifferent protonation equilibria of 4-methylimidazole and acetic acid
Gu, Wei UL; Helms, Volkhard

in Chemphyschem : A European Journal of Chemical Physics and Physical Chemistry (2007), 8(17), 2445-2451

Dynamic protonation equilibria in water of one 4-methylimidazole molecule as well as for pairs and groups consisting of 4-methylimidazole, acetic acid and bridging water molecules are studied using Q-HOP ... [more ▼]

Dynamic protonation equilibria in water of one 4-methylimidazole molecule as well as for pairs and groups consisting of 4-methylimidazole, acetic acid and bridging water molecules are studied using Q-HOP molecular dynamics simulation. We find a qualitatively different protonation behavior of 4-methylimidazole compared to that of acetic acid. On one hand, deprotonoted, neutral 4-methylimidazole cannot as easily attract a freely diffusing extra proton from solution. Once the proton is bound however, it remains tightly bound on a time scale of tens of nanoseconds. In a linear chain composed of acetic acid, a separating water molecule and 4-methylimidazole, an excess proton is equally shared between 4-methylimidozole and water. When a water molecule is linearly placed between two acetic acid molecules, the excess proton is always found on the central water. On the other hand, an excess proton in a 4-methylimidazole-water-4-methylimidozole chain is always localized on one of the two 4-methylimidozoles. These findings are of interest to the discussion of proton transfer along chains of amino acids and water molecules in biomolecules. [less ▲]

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