Adhesive water networks facilitate binding of protein interfaces

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 ▲]

Atomistic Simulation of Water Percolation and Proton Hopping in Nation Fuel Cell Membrane

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 ▲]

Tightly Connected Water Wires Facilitate Fast Proton Uptake at The Proton Entrance of Proton Pumping Proteins

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 ▲]

Different protonation equilibria of 4-methylimidazole and acetic acid

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 ▲]