Surface Topography Effects of Globular Biomolecules on Hydration Water.

Hydration water serves as a microscopic manifestation of structural stability and functions of biomolecules. To develop bio-nanomaterials in applications, it is important to study how the surface topography and heterogeneity of biomolecules result in their diversity of the hydration dynamics and energetics. We here performed molecular dynamics simulations combined with the steered molecular dynamics and umbrella sampling to investigate the dynamics and escape process associated with the free energy change of water molecules close to a globular biomolecule, i.e., hemoglobin (Hb) and G-quadruplex DNA (GDNA). The residence time, power of long-time tail, and dipole relaxation time were found to display drastic changes within the averaged hydration shell of 3.0-5.0 Å. Compared with bulk water, in the inner hydration shell, the water dipole moment displays a slower relaxation process and is more oriented toward GDNA than toward Hb, forming a hedgehog-like structure when it surrounds GDNA. In particular, a spine water structure is observed in the GDNA narrow groove. The water isotope effect not only prolongs the dynamic time scales of libration motion in the inner hydration shell and the dipole relaxation processes in the bulk but also strengthens the DNA spine water structure. The potential of the mean force profile reflects the integrity of the hydration shell structure and enables us to obtain detailed insights into the structures formed by water, such as the caged H-bond network and the edge bridge structures; it also reveals that local hydration shell free energy (LHSFE) depends on H-bond rupture processes and ranges from 0.2 to 4.2 kcal/mol. Our results demonstrate that the surface topography of a biomolecule influences the integrity of the hydration shell structure and LHSFE. Our studies are able to identify various further applications in the areas of microfluid devices and nano-dewetting on bioinspired surfaces.

A model for ultra-fast charge transport in membrane proteins.

Isolated proteins have recently been observed to transport charge and reactivity over very long distances with extraordinary rates and near perfect efficiencies in spite of their site. This is not the case if the peptide is in water, where the efficiency of charge hopping to the next site is reduced to approximately 2%. Here, water is not an ideal solvent for charge transport. The issue at hand is how to explain such enormous charge transfer quenching in water compared to another typical medium, namely lipid. We performed molecular dynamics simulations to computationally substantiate the novel long-distance charge transfer yield of the polypeptides in lipids. This is characterized by the charge transfer persistent-distance decay constant and not by the rate, which is seldom, if ever, measured and hence not directly addressed here. This model can encompass an extremely wide range of yields over very long distances in peptides in various media. The calculations here demonstrate the good charge transport efficiency in lipids in contrast to the poor efficiency in water. The protein charge transport also exhibits a very strong anisotropic effect in lipids. The peptide secondary structure effect of charge transfer in membranes is analyzed in contrast to that in water. These results suggest that this model can be useful for the prediction of charge transfer efficiency in various environments of interest and indicate that the charge transfer is highly efficient in membrane proteins.

Zero kinetic energy spectroscopy: mass-analyzed threshold ionization spectra of chromium sandwich complexes with alkylbenzenes, (η(6)-RPh)(2)Cr (R = Me, Et, i-Pr, t-Bu).

For over 25 years zero kinetic energy (ZEKE) spectroscopy has yielded a rich foundation of high-resolution results of molecular ions. This was based on the discovery in the late 60's of long-lived ion states throughout the ionization continuum of molecular ions. Here, an example is chosen from another fundamental system pioneered at this university. The mass-analyzed threshold ionization (MATI) spectra of jet-cooled chromium bisarene complexes (η(6)-RPh)(2)Cr (R = Me (1), Et (2), i-Pr (3), and t-Bu (4)) have been measured and interpreted on the basis of DFT calculations. The MATI spectra of complexes 1 and 2 appear to reveal features arising from ionizations of the isomers formed by the rotation of one arene ring relative to the other. The 1 and 2 MATI spectra show two intense peaks corresponding to the 0(0)(0) ionizations with inverse intensity ratios. As indicated by the DFT calculations, the intensity ratio change on going from 1 to 2 results from different isomers contributing to each MATI peak. The ionization energies corresponding to the 0(0)(0) peaks are 42746 ± 5 and 42809 ± 5 cm(-1) for compound 1 and 42379 ± 5 and 42463 ± 5 cm(-1) for complex 2. The 1 and 2 spectra show also the weaker features representing transitions to the vibrationally excited cationic levels, the signals of individual rotamers being detected and assigned on the basis of calculated vibrational frequencies. The MATI spectra of compounds 3 and 4 reveal only one strong peak because of close ionization potentials of the isomers contributing to the MATI signal. The 3 and 4 ionization energies are 42104 ± 5 and 41917 ± 5 cm(-1), respectively. The precise values of ionization energies obtained from the MATI spectra reveal a nonlinear dependence of the IE on the number of Me groups in the alkyl substituents of (η(6)-RPh)(2)Cr. This can be explained by an increase in the molecular zero point energies on methylation of the substituents.

Hydrogen bonds in membrane proteins.

Hydrogen 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, we performed molecular dynamics simulations of these fluctuating hydrogen bonds. This indicated long-range entropy and energy contributions extending far into the liquid environment. The results showed that the binding of a given hydrogen bond is much reduced as a result of these interactions in water, as is required for biological activity and in very good confirmation of known experimental results. The larger water environment directly interacts with the hydrogen bond essentially due to long-range molecular interactions. Such a substantial lowering of the energy of the hydrogen bond in water brings it into the range of activation by many biological processes ( Sheu et al. Chem. Phys. Lett. 2008 , 462 , 1 - 5 ). Thus, the water medium profoundly increases the rate. Furthermore, very large entropic changes are associated with the rupture of hydrogen bonds in water, whereas no such effects are seen for the isolated molecule. Interestingly, such an increase in rates in water is still accompanied by a large negative change in entropy in the extended solvent environment, and this reduces the rate by some 2 orders of magnitude. Recent molecular dynamics experiments in D(2)O substantiate this model and show a large solvent isotope effect. In this work, we used lipids as the environment for the hydrogen bond and discovered that the energy is also reduced from that found in the isolated molecule, but not as far as in water. On the other hand, we found that no entropy penalty exists for breaking the hydrogen bond in lipids, as seen for water. These two effects compensate, even though the energy is some 2 times larger. The entropic penalty is reduced such that the rate is higher than in water despite the higher energy. This is a significant result for understanding the reactivity and dynamics of proteins in lipids. It should be noted that these are very important solvent effects on entropies and free energies that are not usually reflected in statistical thermodynamic computations for reactants and products. The very long-range effect of the solvent makes substantial contributions to kinetic rate constants and is readily evaluated in this kinetic method. To ignore these long-range environmental effects on the entropy can lead to very spurious results when calculating rates of protein mobilities. Hence, the results not only agree very well with the known hydrogen-bond energies directly as a result of various environmental factors, but even correctly predict a phase transition in the lipid.

Distal charge transport in peptides.

Biological systems often transport charges and reactive processes over substantial distances. Traditional models of chemical kinetics generally do not describe such extreme distal processes. In this Review, an atomistic model for a distal transport of information, which was specifically developed for peptides, is considered. Chemical reactivity is taken as the result of distal effects based on two-step bifunctional kinetics involving unique, very rapid motional properties of peptides in the subpicosecond regime. The bifunctional model suggests highly efficient transport of charge and reactivity in an isolated peptide over a substantial distance; conversely, a very low efficiency in a water environment was found. The model suggests ultrafast transport of charge and reactivity over substantial molecular distances in a peptide environment. Many such domains can be active in a protein.

Two-color resonance-enhanced multiphoton ionization study of the lowest Rydberg p state of bis(eta6-benzene)chromium and its deuterated derivatives.

Two-color resonance-enhanced multiphoton ionization (REMPI) spectra of jet-cooled (eta(6)-C(6)H(6))(2)Cr(1), (eta(6)-C(6)D(6))(2)Cr(2), and (eta(6)-C(6)D(6))(eta(6)-C(6)D(5)H)Cr(3) have been measured with use of the 3d(z)2-->R4p(x,y) Rydberg transition as the first step of the electronic excitation. The 0(0) (0) Rydberg component shifts by 59 and 54 cm(-1) to red when one goes from 1 to 2 and 3, respectively. Surprisingly, the REMPI spectra of 1-3 show very rich vibronic structures revealing both totally symmetric vibrations and degenerate vibrational modes. Presence of intense peaks corresponding to the e(2g) modes in the spectra of 1 and 2 is indicative of Jahn-Teller coupling in the R4p(x,y) Rydberg state. Additional REMPI resonances appear on going from 1 and 2 to 3 as a result of the symmetry reduction. The vibronic components in the spectra of 1-3 were assigned on the basis of the selection rules and comparison with the vibrational frequencies of the 1 and 2 ground-state molecules. The frequencies of over 10 normal vibrations have been determined for the gas-phase 1-3 Rydberg-state molecules from the REMPI experiment. The wavenumber corresponding to the lowest-energy mode (the ring torsion vibration) appears to be 40 cm(-1) in 1 and 35 cm(-1) in the deuterated complexes. The REMPI peaks are homogeneously broadened. The lower lifetime limits for the upper-state components increase on going from the vibrationless level to higher-lying vibronic states and on going from 1 to the deuterated derivatives.

A novel mechanism of proton transfer in protonated peptides.

The study presents quantum-chemical calculations on proton transfer in protonated N-acetylglycyl-N1-methylglycinamide (AGA) as a short oligopeptide model. All calculations employ the B3LYP functional and the 6-31++G** basis set. Two different mechanisms of proton transfer are discussed. The rate-determining step of the first mechanism exhibits an energy barrier of about 17.7 kcal mol-1, and it is represented by an isomerization of the proton around the double bond of the carbonyl group. The second mechanism is based on the large conformational flexibility of AGA, where all carbonyl oxygens cooperate. The rate-determining step of this mechanism exhibits an energy barrier of only 8.3 kcal mol-1.