The effect of entropy on protein hydrogen bonds

Hydrogen bonds are essential elements in protein structure and dynamics. We show that such bonds are strongly dominated by entropic contributions of the environment that can be at least as important as energetic considerations. These contributions are global in that they are not due to the internal degrees of freedom. The mol. dynamics (MD) is carried out as a computer expt. and agrees very well with the known energies of hydrogen bonds, both in water and in the isolated mol. The entropy in water as a solvent is found to modulate the hydrogen bond breaking and reformation rate by two orders of magnitude, in a neg. direction. [on SciFinder(R)

Hydrogen bonds in membrane proteins

H-bonds are essential tie points inside protein structures. They undergo dynamic rupture and rebonding processes on the time scale of tens of picoseconds. Proteins can partially rearrange during such ruptures. In previous work, the authors performed mol. dynamics simulations of these fluctuating H-bonds. This indicated long-range entropy and energy contributions extending far into the liq. environment. The results showed that the binding of a given H-bond was much reduced as a result of these interactions in water, as was required for biol. activity and in very good confirmation of known exptl. results. The larger water environment directly interacted with the H-bond essentially due to long-range mol. interactions. Such a substantial lowering of the energy of the H-bond in water brought it into the range of activation by many biol. processes. Thus, the water medium profoundly increases the rate. Furthermore, very large entropic changes were assocd. with the rupture of H-bonds in water, whereas no such effects were seen for the isolated mol. Interestingly, such an increase in rates in water was still accompanied by a large neg. change in entropy in the extended solvent environment, and this reduced the rate by some 2 orders of magnitude. Recent mol. dynamics expts. in D2O substantiated this model and showed a large solvent isotope effect. Here, the authors used lipids as the environment for the H-bond and discovered that the energy was also reduced from that found in the isolated mol., but not as far as in water. On the other hand, it was found that no entropy penalty existed for breaking the H-bond in lipids, as seen for water. These 2 effects compensated, even though the energy was ∼2-fold larger. The entropic penalty was reduced such that the rate was higher than in water despite the higher energy. This was a significant result for understanding the reactivity and dynamics of proteins in lipids. It should be noted that these were very important solvent effects on entropies and free energies that were not usually reflected in statistical thermodn. computations for reactants and products. The very long-range effect of the solvent made substantial contributions to kinetic rate consts. and was readily evaluated in this kinetic method. To ignore these long-range environmental effects on the entropy can lead to very spurious results when calcg. rates of protein mobilities. Hence, the results not only agree very well with the known H-bond energies directly as a result of various environmental factors, but even correctly predict a phase transition in the lipid. [on SciFinder(R)

Molecular Dynamics of Hydrogen Bonds in Protein-D2O: The Solvent Isotope Effect

We suggest that the H-bond in proteins not only mirrors the motion of hydrogen in its own atomistic setting but also finds its origin in the collective environment of the hydrogen bond in a global lattice of surrounding H2O mols. This water lattice is being perturbed in its optimal entropic configuration by the motion of the H-bond. Furthermore, bonding interaction with the lattice drop the H-bond energy from some 5 kcal/mol for the pure protein in the absence of H2O, to some 1.6 kcal/mol in the presence of the H2O medium. This low value here is detd. in a computer expt. involving MD calcns. and is a value close to the generally accepted value for biol. systems. In accordance with these computer expts. under ambient conditions, the H-bond energy is seriously depressed, hence confirming the subtle effect of the H2O medium directly interacting with the H-bond and permitting a strong fluxional behavior. Furthermore, water produces a very large change in the entropy of activation due to the hydrogen bond breakage, which affects the rate by as much as 2 orders of magnitude. We also observe that there is an entire ensemble of H-bond structures, rather than a single transition state, all of which contribute to this H-bond. Here the model is tested by changing to D2O as the surrounding medium resulting in a substantial solvent isotope effect. This demonstrates the important influence of the environment on the individual hydrogen bond. [on SciFinder(R)

Charge transport in a polypeptide chain

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