References of "Gu, Wei 50001901"
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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 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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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 detailMolecular dynamics simulation of truncated bovine adrenodoxin
Shakya, S. K.; Gu, Wei UL; Helms, V.

in Biopolymers (2005), 78(1), 9-20

The 128 amino acid long soluble protein adrenodoxin (Adx) is a typical member of the ferredoxin protein family that are electron carrier proteins with an iron-sulfur cofactor. Adx carries electrons from ... [more ▼]

The 128 amino acid long soluble protein adrenodoxin (Adx) is a typical member of the ferredoxin protein family that are electron carrier proteins with an iron-sulfur cofactor. Adx carries electrons from adrenodoxin reductase (AdR) to cytochrome P450s. Its binding modes to these proteins were previously characterized by site-directed mutagenesis, by X-ray crystallography for the complex Adx:AdR, and by NMR. However, no clear evidence has been provided for the driving force that promotes Adx detachment from AdR upon reduction. Here, we characterized the conformational dynamics of unbound Adx in the oxidized and reduced forms using 2-20 ns long molecular dynamics simulations. The most noticeable difference between both forms is the enhanced flexibility of the loop (47-51) surrounding the iron-sulfur cluster in the reduced form. Together with several structural displacements at the binding interface, this increased flexibility may be the key factor promoting unbinding of reduced Adx from AdR. This points to an intrinsic property of reduced Adx that drives dissociation. (c) 2005 Wiley Periodicals, Inc. [less ▲]

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See detailAre solvation free energies of homogeneous helical peptides additive?
Staritzbichler, R.; Gu, Wei UL; Helms, V.

in Journal of Physical Chemistry B (2005), 109(40), 19000-19007

We investigated the additivity of the solvation free energy of amino acids in homogeneous helices of different length in water and in chloroform. Solvation free energies were computed by ... [more ▼]

We investigated the additivity of the solvation free energy of amino acids in homogeneous helices of different length in water and in chloroform. Solvation free energies were computed by multiconfiguration thermodynamic integration involving extended molecular dynamics simulations and by applying the generalized-born surface area solvation model to static helix geometries. The investigation focused on homogeneous peptides composed of uncharged amino acids, where the backbone atoms are kept fixed in an ideal helical conformation. We found nonlinearity especially for short peptides, which does not allow a simple treatment of the interaction of amino acids with their surroundings. For homogeneous peptides longer than five residues, the results from both methods are in quite good agreement and solvation energies are to a good extent additive. [less ▲]

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See detailCyclophilin a binds to linear peptide motifs containing a consensus that is present in many human proteins
Piotukh, K.; Gu, Wei UL; Kofler, M. et al

in Journal of Biological Chemistry (2005), 280(25), 23668-23674

Cyclophilin A ( CypA) is a peptidyl-prolyl cis/trans-isomerase that is involved in multiple signaling events of eukaryotic cells. It might either act as a catalyst for prolyl bond isomerization, or it can ... [more ▼]

Cyclophilin A ( CypA) is a peptidyl-prolyl cis/trans-isomerase that is involved in multiple signaling events of eukaryotic cells. It might either act as a catalyst for prolyl bond isomerization, or it can form stoichiometric complexes with target proteins. We have investigated the linear sequence recognition code for CypA by phage display and found the consensus motif FGPXLp to be selected after five rounds of panning. The peptide FGP-DLPAGD showed inhibition of the isomerase reaction and NMR chemical shift mapping experiments highlight the CypA interaction epitope. Ligand docking suggests that the peptide was able to bind to CypA in the cis- and trans-conformation. Protein Data Bank searches reveal that many human proteins contain the consensus motif, and several of these protein motifs are shown to interact with CypA in vitro. These sequences represent putative target sites for binding of CypA to intracellular proteins. [less ▲]

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See detailAlternative binding modes of proline-rich peptides binding to the GYF domain
Gu, Wei UL; Kofler, M.; Antes, I. et al

in Biochemistry (2005), 44(17), 6404-6415

Recognition of proline-rich sequences plays an important role for the assembly of multiprotein complexes during the course of eukaryotic signal transduction and is mediated by a set of protein folds that ... [more ▼]

Recognition of proline-rich sequences plays an important role for the assembly of multiprotein complexes during the course of eukaryotic signal transduction and is mediated by a set of protein folds that share characteristic features. The GYF (glycine-tyrosine-phenylalanine) domain is known as a member of the superfamily of recognition domains for proline-rich sequences. Recent studies on the complexation of the CD2BP2-GYF domain with CD2 peptides showed that the peptide adopts an extended conformation and forms a polyproline type-II helix involving residues Pro4-Pro7 [Freund et al. (2002) EMBO J. 21, 5985-5995]. R/K/GxxPPGxR/K is the key signature for the peptides that bind to the GYF domain [Kofler et at. (2004) J. Biol. Chem. 279, 28292-28297]. In our combined theoretical and experimental study, we show that the peptides adopt a polyproline 11 helical conformation in the unbound form as well as in the complex. From molecular dynamics simulations, we identify a novel binding mode for the G8W mutant and the wild-type peptide (shifted by one proline in register). In contrast, the conformation of the peptide mutant H9M remains close to the experimentally derived wild-type GYF-peptide complex. Possible functional implications of this altered conformation of the bound ligand are discussed in the light of our experimental and theoretical results. [less ▲]

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See detailDynamical binding of proline-rich peptides to their recognition domains
Gu, Wei UL; Helms, V.

in Biochimica et Biophysica Acta-Proteins and Proteomics (2005), 1754(1-2), 232-238

Recognition of proline-rich sequences plays an important role for the assembly of multi-protein complexes during the course of eukaryotic signal transduction and is mediated by a set of protein folds that ... [more ▼]

Recognition of proline-rich sequences plays an important role for the assembly of multi-protein complexes during the course of eukaryotic signal transduction and is mediated by a set of protein folds that share characteristic features. For many complex systems containing proline-rich sequences, multiple binding modes have been found by theoretical and/or experimental studies. In this review, we discuss the different binding modes as well as the correlated dynamics of the peptides and their recognition domains, and some implications to their biological functions. Further-more, we give an outlook of the systems in the context of systems biology. (c) 2005 Elsevier B.V. All rights reserved. [less ▲]

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See detailSolvation free energies and transfer free energies for amino acids from hydrophobic solution to water solution from a very simple residue model
Gu, Wei UL; Rahi, S. J.; Helms, V.

in Journal of Physical Chemistry B (2004), 108(18), 5806-5814

Solvation free energies of neutral amino acids in water and in chloroform were computed from extensive molecular dynamics simulations using multiconfiguration thermodynamic integration. The values ... [more ▼]

Solvation free energies of neutral amino acids in water and in chloroform were computed from extensive molecular dynamics simulations using multiconfiguration thermodynamic integration. The values computed for the AMBER force field are in very good agreement with available experimental data (rms differences of 5.1 kJ mol(-1) for the solvation free energies and 6.4 kJ mol(-1) for the transfer free energies of amino acids between water and chloroform) and with existing calculations. We derived an additive residue-scale solvation model formulated as the sum of a nonpolar term that is proportional to the molecular surface area and an electrostatic term (Kirkwood-Onsager model) for the hydration free energy of a dipole in a solvated cavity. This model can surprisingly well describe the solvation free energies in water and chloroform as well as the transfer free energies of amino acids between the two solvents when suitably adapted cavity radii are used. Root-mean-square differences of the predicted values with respect to the values calculated from thermodynamic integration are 1.8, 5.9, and 7.7 kJ mol(-1), respectively. [less ▲]

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See detailMolecular dynamics simulation of the unfolding of the human prion protein domain under low pH and high temperature conditions
Gu, Wei UL; Wang, T. T.; Zhu, J. et al

in Biophysical Chemistry (2003), 104(1), 79-94

Four 10-ns molecular dynamics (MD) simulations of the human prion protein domain (HuPrP 125-228) in explicit water solution have been performed. Each of the simulations mimicked a different environment of ... [more ▼]

Four 10-ns molecular dynamics (MD) simulations of the human prion protein domain (HuPrP 125-228) in explicit water solution have been performed. Each of the simulations mimicked a different environment of the protein: the neutral pH environment was simulated with all histidine residues neutral and bearing a ND proton and with other titratable side chains charged, the weakly acidic environment was simulated with all titratable side chains charged, he strongly acidic environment was simulated with all titratable side chains protonated. The protein in neutral pH environment was simulated at both ambient (298 K) and higher (350 K) temperatures. The native fold is stable in he neutral pH/ambient temperature simulation. Through out all other simulations, a quite stable core consisted of 0-20 residues around the disulfide bond retain their initial conformations. However, the secondary structures of the Protein show changes of various degrees compared to the native fold, parts of the helices unfolded and the beta-sheets extended. Our simulations indicated that the heat-induced unfolding and acid-induced unfolding of HuPrP might follow different pathways: the initial stage of the acid-induced unfolding may include not only changes in secondary structures, but also changes in the tertiary structures. Under the strongly acidic condition, obvious tertiary structure changes take place after 10-ns simulation, the secondary structure elements and the loops becoming more parallel to each other, resulting in a compact state, which was stabilized by a large number of new, non-native side chain-side chain contacts. Such tertiary structure changes were not observed in the higher temperature simulation, and intuitively, they may favor the further extension of the beta-sheets and eventually the agglomeration of multiple protein molecules. The driving forces for this tertiary structure changes are discussed. Two additional 10-ns MD simulations, one with Asp202 protonated and the other with Glu196 protonated compared to the neutral pH simulation, were carried out. The results showed that the stability of the native fold is very subtle and can be strongly disturbed by eliminating a single negative charge at one of such key sites. Correlations of our results with previous experimental and theoretical studies are discussed. (C) 2003 Elsevier Science B.V. All rights reserved. [less ▲]

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