Entropy of water in the hydration layer of major and minor grooves of DNA

Transport properties (translational and rotational) of water in the two grooves of the B-DNA duplex are known to be different from those in the bulk. Here, we use a recently developed theoretical scheme to compute the entropies of water molecules in both of the grooves of DNA and compare them with that in the bulk. The scheme requires as input both translational and rotational velocity autocorrelation function (C(V)(t) and C(omega)(t), respectively) data. These velocity autocorrelation functions were computed from an atomistic MD simulation of a B-DNA duplex (36 base pairs long) in explicit water (TIP3P). The average values of the entropy of water at 300 K in both of the grooves of DNA (the TS value in the major groove is 6.71 kcal/mol and that in the minor groove is 6.41 kcal/mol) are found to be significantly lower than that in bulk water (the TS value is 7.27 kcal/mol). Thus, the entropic contribution to the free energy change (TDeltaS) of transferring a minor groove water molecule to the bulk is 0.86 kcal/mol and of transferring a major groove water to the bulk is 0.56 kcal/mol at 300 K, which is to be compared with 1.44 kcal/mol for melting of ice at 273 K. We also calculate the energy of interaction of each water molecule with the rest of the atoms in the system and hence calculate the chemical potential (Helmholtz free energy per water molecule, A = E - TS) in the different domains. The identical free energy value of water molecules in the different domains proves the robustness of the scheme. We propose that the configurational entropy of water in the grooves can be used as a measure of the mobility (or microviscosity) of water molecules in a given domain.     

Hydrogen bond and residence dynamics of ion-water and water-water pairs in supercritical aqueous ionic solutions: dependence on ion size and density

We have carried out a series of molecular dynamics simulations to investigate the hydrogen bond and residence dynamics of X(-)-water (X=F, Cl, and I) and pairs in aqueous solutions at a temperature of 673 K. The calculations are done at six different water densities ranging from 1.0 to 0.15 g cm(-3). The hydrogen bonds are defined by using a set of configurational criteria with respect to the anion(oxygen)-oxygen and anion(oxygen)-hydrogen distances and the anion(oxygen)-oxygen-hydrogen angle for an anion(water)-water pair. The F(-)-water hydrogen bonds are found to have a longer lifetime than all other hydrogen bonds considered in the present study. The lifetime of Cl(-)-water hydrogen bonds is shorter than that of F(-)-water hydrogen bonds but longer than the lifetime of water-water hydrogen bonds. The lifetimes of I(-)-water and water-water hydrogen bonds are found to be very similar. Generally, the lifetimes of both anion-water and water-water hydrogen bonds are found to be significantly shorter than those found under ambient conditions. In addition to hydrogen bond lifetimes, we have also calculated the residence times and the orientational relaxation times of water molecules in ion(water) hydration shells and have discussed the correlations of these dynamical quantities with the observed dynamics of anion(water)-water hydrogen bonds as functions of the ion size and density of the supercritical solutions.     

Description of collective effects in computer models of water

The dynamics of a system containing 3456 water molecules in a cubic cell with periodic boundary conditions at 297 K was simulated. The time dependence of distances between oxygen atoms was examined for many pairs of molecules. These distances often oscillate around a certain average value over long periods of time (10 ps and longer). These average values can be about 2.8 Å (hydrogen bond) or much larger, up to 12–13 Å and more. This suggests that big groups of molecules are involved in a concerted motion. Lists of hydrogen bonds in 50 configurations divided by an interval of about 1 ps are compared. The average lifetime of a hydrogen bond is about 7 ps. The network of hydrogen bonds is colored according to their lifetimes for one of the configurations. The bonds that live longer than 7 ps form an infinite cluster. The bonds that live longer than 8 ps join to form a great number of finite clusters including several hundreds of nodes (molecules). These clusters contain few closed cycles. Even the bonds that live longer than 20 ps are united into clusters each containing two or three nodes (molecules). The self-diffusion coefficient for molecules involved in long-lived bonds is likely to be slightly smaller than that for molecules which do not participate in these bonds.     

Direct observation of essential DNA dynamics: melting and reformation of the DNA minor groove

The dynamics of bound water and ions present in the minor groove of a dodecamer DNA has been decoupled from that of the long-range twisting/bending of the DNA backbone, using the minor groove binder Hoechst 33258 as a fluorescence reporter in the picosecond-resolved time window. The bound water and ions are essential structural components of the minor groove and are destroyed with the destruction of the minor groove when the dodecamer melts at high temperatures and reforms on subsequent cooling of the melted DNA. The melting and rehybridization of the DNA has been monitored by the changes in secondary structure using circular dichroism (CD) spectroscopy. The change in the relaxation dynamics of the DNA has been studied with picosecond resolution at different temperatures, following the temperature-dependent melting and rehybridization profile of the dodecamer, using time-resolved emission spectra (TRES). At room temperature, the relaxation dynamics of DNA is governed by a 40 ps (30%) and a 12.3 ns (70%) component. The dynamics of bound water and ions present in the minor groove is characterized by the 40 ps component in the relaxation dynamics of the probe bound in the minor groove of the dodecamer DNA. Analyses of the TRES taken at different temperatures show that the contribution of this component decreases and ultimately vanishes with the destruction of the minor groove and reappears again with the reformation of the groove. The dynamical behavior of bound water molecules and ions of a genomic DNA (from salmon testes) at different temperatures is also found to be consistent with that of the dodecamer. The longer component of approximately 10 ns in the DNA dynamics is found to be associated with the long-range bending/twisting of the DNA backbone and the associated counterions. The transition from bound water to free water at the DNA surface, indicative of the change in the hydration number associated with each base pair, has also been ascertained in the case of the genomic DNA at different temperatures by employing densimetric and acoustic techniques.     

Multiple time scales in solvation dynamics of DNA in aqueous solution: the role of water, counterions, and cross-correlations

Recent time domain experiments have explored solvation dynamics of a probe located inside a DNA duplex, in an effort to gain information, e.g., on the dynamics of water molecules in the DNA major and minor grooves and their environment. Multiple time constants in the range of a few picoseconds to several nanoseconds were obtained. We have carried out 15 ns long atomistic molecular dynamics simulations to study the solvation dynamics of bases of a 38 base-pair long DNA duplex in an aqueous solution containing counterions. We have computed the energy-energy time correlation function (TCF) of the four individual bases (A, T, G, and C) to characterize the solvation dynamics. All the TCFs display highly nonexponential decay with time. When the trajectories are analyzed with 100 fs time resolution, the TCF of each base shows initial ultrafast decay (with tau1 approximately equal 60-80 fs) followed by two intermediate components (tau2 approximately equal 1 ps, tau3 approximately equal 20-30 ps), in near complete agreement with a recent time domain experiment on DNA solvation. Interestingly, the solvation dynamics of each of the four different nucleotide bases exhibit rather similar time scales. To explore the existence of slow relaxation at longer times reported recently in a series of experiments, we also analyzed the solvation TCFs calculated with longer time trajectories and with a larger time resolution of 1 ps. In this case, an additional slow component with a time constant of the order of 250 ps is observed. Through an analysis of partial solvation TCFs, we find that the slow decay originates mainly from the interaction of the nucleotides with the dipolar water molecules and the counterions. An interesting negative cross-correlation between water and counterions is observed, which makes an important contribution to relaxation at intermediate to longer times.     

A first principles molecular dynamics study of lithium atom solvation in binary liquid mixture of water and ammonia: structural, electronic, and dynamical properties

The preferential solvation of solutes in mixed solvent systems is an interesting phenomenon that plays important roles in solubility and kinetics. In the present study, solvation of a lithium atom in aqueous ammonia solution has been investigated from first principles molecular dynamics simulations. Solvation of alkali metal atoms, like lithium, in aqueous and ammonia media is particularly interesting because the alkali metal atoms release their valence electrons in these media so as to produce solvated electrons and metal counterions. In the present work, first principles simulations are performed employing the Car-Parrinello molecular dynamics method. Spontaneous ionization of the Li atom is found to occur in the mixed solvent system. From the radial distribution functions, it is found that the Li(+) ion is preferentially solvated by water and the coordination number is mostly four in its first solvation shell and exchange of water molecules between the first and second solvation shells is essentially negligible in the time scale of our simulations. The Li(+) ion and the unbound electron are well separated and screened by the polar solvent molecules. Also the unbound electron is primarily captured by the hydrogens of water molecules. The diffusion rates of Li(+) ion and water molecules in its first solvation shell are found to be rather slow. In the bulk phase, the diffusion of water is found to be slower than that of ammonia molecules because of strong ammonia-water hydrogen bonds that participate in solvating ammonia molecules in the mixture. The ratio of first and second rank orientational correlation functions deviate from 3, which suggests a deviation from the ideal Debye-type orientational diffusion. It is found that the hydrogen bond lifetimes of ammonia-ammonia pairs is very short. However, ammonia-water H-bonds are found to be quite strong when ammonia acts as an acceptor and these hydrogen bonds are found to live longer than even water-water hydrogen bonds.     

NMR structural analysis of a modular threading tetraintercalator bound to DNA

The synthesis and NMR structural studies are reported for a modular threading tetraintercalator bound to DNA. The tetraintercalator design is based on 1,4,5,8-tetracarboxylic naphthalene diimide units connected through flexible peptide linkers. Aided by an overall C(2) symmetry, NMR analysis verified a threading polyintercalation mode of binding, with linkers alternating in the order minor groove, major groove, minor groove, analogous to how a snake might climb a ladder. This study represents the first NMR analysis of a threading tetraintercalator and, as such, structurally characterizes a new topology for molecules that bind to relatively long DNA sequences with extensive access to both DNA grooves.     

Hydrogen bond lifetime dynamics at the interface of a surfactant monolayer

The dynamics of water near the polar headgroups of surfactants in a monolayer adsorbed at the air/water interface is likely to play a decisive role in determining the physical behavior of such organized assemblies. We have carried out an atomistic molecular dynamics (MD) simulation of a monolayer of the anionic surfactant sodium bis(2-ethyl-1-hexyl) sulfosuccinate (aerosol-OT or AOT) adsorbed at the air/water interface. The simulation is performed at room temperature with a surface coverage of that at the critical micelle concentration (78 Angstrom(2)/molecule). Detailed analyses of the lifetime dynamics of surfactant-water (SW) and water-water (WW) hydrogen bonds at the interface have been carried out. The nonexponential hydrogen bond lifetime correlation functions have been analyzed by using the formalism of Luzar and Chandler, which allowed identification of the bound states at the interface and quantification of the dynamic equilibrium between bound and quasi-free water molecules, in terms of time-dependent relaxation rates. It is observed that the water molecules present in the first hydration layer form strong hydrogen bonds with the surfactant headgroups and hence have longer lifetimes. Importantly, it is found that the overall relaxation of the SW hydrogen bonds is faster for those water molecules which form two hydrogen bonds with the surfactant headgroups than those forming one such hydrogen bond. Equally interestingly, it is further noticed that water molecules beyond the first hydration layer form weaker hydrogen bonds than pure bulk water.     

Coherent molecular motion in aquatic environment. Extraction of correlation from noise

Molecular dynamics simulation of liquid water and system “argon-thin water film” has been performed. In was shown that time dependence of distances between oxygen atoms of water molecules, connected by hydrogen bonds, looks like random noise and these molecules are doomed to move concertedly. The average distance between the argon atoms dissolved in water is retained for some time, so the argon atoms included in the hydrogen bond networks, but not capable to participate in hydrogen bonds are involved in concerted motions. The problem of revealing the correlations in the motion of molecules and atoms is discussed.     

Computational investigation of the role of hydration in nucleic acid structure and function

The results of the Monte Carlo Metropolis simulation of water structure and of the hydration of nucleic acid fragments, complementary base pairs and mispairs, base pair stacks, and duplex fragments have been summarized. Systematic investigations suggest some general conclusions: (1) the hydration shell structure of the major and minor grooves of the duplex depends significantly on DNA conformation (or stack configuration) and nucleotide sequence, while global hydration characteristics (average energy, the number of water–water and water–base H-bonds) are only slightly dependent on these factors, (2) hydration economy takes place in the B–A transition due to an increase of the number of water molecules forming hydrogen bonds with two or more atoms of bases (water bridging), and (3) the hydration of the duplex could contribute to nucleic acid functioning via water-bridged mispair formation and stabilization of specific conformations.     

Solvation structure of hydroxyl radical by Car-Parrinello molecular dynamics

Car-Parrinello molecular dynamics simulations of a hydroxyl radical in liquid water have been performed. Structural and dynamical properties of the solvated structure have been studied in details. The partial atom-atom radial distribution functions for the hydrated hydroxyl do not show drastic differences with the radial distribution functions for liquid water. The OH is found to be a more active hydrogen bond donor and acceptor than the water molecule, but the accepted hydrogen bonds are much weaker than for the hydroxide OH- ion. The first solvation shell of the OH is less structured than the water's one and contains a considerable fraction of water molecules that are not hydrogen bonded to the hydroxyl. Part of them are found to come closer to the solvated radical than the hydrogen bonded molecules do. The lifetime of the hydrogen bonds accepted by the hydroxyl is found to be shorter than the hydrogen bond lifetime in water. A hydrogen transfer between a water molecule and the OH radical has been observed, though it is a much rarer event than a proton transfer between water and an OH- ion. The velocity autocorrelation power spectrum of the hydroxyl hydrogen shows the properties both of the OH radical in clusters and of the OH- ion in liquid.     

Finding potential DNA-binding compounds by using molecular shape

Summary For the first time a general shape-search docking algorithm (DOCK) has been applied to the minor and major grooves of A-, B- and Z-type DNA dodecamers and to an intercalation site in a B-DNA-type hexamer. Both experimentally and theoretically derived geometries for the various DNA fragments were used. The DOCK searches were carried out on a subset of the Cambridge Crystallographic Database, consisting of almost 10 000 molecules. One of the molecules that scored best in terms of the DOCK algorithm was CC-1065, a potent antitumor agent known to (covalently) bind the AT-rich parts of the minor groove of B-DNA. Several known DNA-binding agents also scored highly. Molecules with shapes complementary to A-, B- and Z-type DNA were indicated by DOCK. In addition, compounds were extracted from the database that might be selective for the GC-rich regions of the minor groove of B-DNA. Many of the compounds in the present study may serve as a starting point for further molecular design of novel DNA-binding ligands.     

Combined use of Overhauser spectroscopy and NMR diffusion experiments for mapping the hydration structure of nucleosides: structure and dynamics of uridine in water

Complementary results from 13C intermolecular nuclear Overhauser effects (NOE), 1H-13C heteronuclear Overhauser spectroscopy (HOSEY) and 1H-NMR diffusion measurements were used for probing the structure of the first solvation shell of uridine in water. It is demonstrated that a cyclic dihydrate is formed. The two water molecules produce two hydrogen bonds with the two oxygen atoms from the pyrimidine ring and accept only one hydrogen bond from the amide proton. The dihydrate has only a short lifetime as compared with the rotational correlation time of the free nucleoside. The chemical exchange constant of the amide proton with water is then estimated by diffusion experiments. The results are consistent with previous data obtained for uracil in water and provide interesting information about water accessibility in nucleic acid bases.     

Molecular Dynamics Simulation of Diffusion of Vitamin C in Water Solution

Under different temperatures and concentrations, the diffusion of Vitamin C (VC) in water solution was examined by molecular dynamics simulation. The diffusion coefficients were calculated based on the Einstein equation. The influences of temperature, concentration, and simulation time on the diffusion coefficient were discussed. The results showed that at higher temperature and lower concentration the normal diffusions appear relatively late, but the linear range of mean square displacement curves continues longer than that at lower temperature and higher concentration. At the same temperature, the normal diffusion time increases and the diffusion coefficient decreases as the simulation concentration increases. These simulation results are in good agreement with experiments. Analyses of the pair correlation functions of the simulation systems showed that hydrogen bonds are mainly formed between the hydrogen atoms of VC molecules and oxygen atoms of H₂O molecules, rather than between the O atoms of VC molecules and H atoms of H₂O molecules. The diffusion coefficient is higher as the interaction between water molecules and VC molecules is stronger when VC concentration is lower. The water in the model systems affects the diffusion of VC molecules by the short‐range repulsion of O(H₂O)‐O(H₂O) pairs and the non‐bond interaction of H(H₂O)‐H(H₂O) pairs. The short‐range repulsion of O(H₂O)‐O(H₂O) pairs is greater when VC concentration is higher, the diffusion of VC is weaker. The greater the non‐bond interaction of H(H₂O)‐H(H₂O) pairs is, the higher the VC diffusion is. It is expected that this study can provide a theoretical direction for the experiments on the mass transfer of VC in water solution.     

Differential solvation and tautomer stability of a model base pair within the minor and major grooves of DNA

2-(2'-Hydroxyphenyl)benzoxazole (HBO) may be used as a model base pair to study solvation, duplex environment, and tautomerization within the major and minor groves of DNA duplexes. In its ground state, HBO possesses an enol moiety which may be oriented syn or anti relative to the imino nitrogen of the benzoxazole ring. In the absence of external hydrogen-bond donors and acceptors HBO exists as the internally hydrogen-bonded syn-enol, a mimic of the rare base pair tautomer found in DNA, which may be photoinduced to tautomerize and form the keto tautomer, a mimic of the dominant base pair tautomer. Previously, we demonstrated that when incorporated into DNA such that the enol moiety is positioned in the major groove, HBO is not solvated, exists exclusively as the internally hydrogen-bonded syn-enol which is efficiently photoinduced to tautomerize, and the corresponding keto tautomer is preferentially stabilized. In stark contrast, we now show that when HBO is incorporated in DNA such that the enol moiety is positioned in the minor groove, the enol tautomer is preferentially stabilized. Molecular dynamics simulations suggest that this results from the formation of a stable hydrogen-bond between the HBO enol and the O4' atom of an adjacent nucleotide, an H-bond acceptor that is only available in the minor groove. The differential stabilization of the enol and keto tautomers in the major and minor grooves may reflect the functions for which these environments evolved, including duplex replication, stability, and recognition.     

Hydrogen bond dynamics and water structure in glucose-water solutions by depolarized Rayleigh scattering and low-frequency Raman spectroscopy

The effect of glucose on the relaxation process of water at picosecond time scales has been investigated by depolarized Rayleigh scattering (DRS) experiments. The process is assigned to the fast hydrogen bonding dynamics of the water network. In DRS spectra this contribution can be safely separated from the slower relaxation process due to the sugar. The detected relaxation time is studied at different glucose concentrations and modeled considering bulk and hydrating water contributions. As a result, it is found that in diluted conditions the hydrogen bond lifetime of proximal water molecules becomes about three times slower than that of the bulk. The effect of the sugar on the hydrogen bond water structure is investigated by analyzing the low-frequency Raman (LFR) spectrum sensitive to intermolecular modes. The addition of glucose strongly reduces the intensity of the band at 170 cm(-1) assigned to a collective stretching mode of water molecules arranged in cooperative tetrahedral domains. These findings indicate that proximal water molecules partially lose the tetrahedral ordering typical of the bulk leading to the formation of high density environments around the sugar. Thus the glucose imposes a new local order among water molecules localized in its hydration shell in which the hydrogen bond breaking dynamics is sensitively retarded. This work provides new experimental evidences that support recent molecular dynamics simulation and thermodynamics results.     

Hydrogen bond dynamics and microscopic structure of confined water inside carbon nanotubes

We have investigated the density and temperature dependences of microscopic structure and hydrogen bond dynamics of water inside carbon nanotubes (CNTs) using molecular dynamics simulation. The CNTs are treated as rigid, and smoothly truncated extended simple point charge water model is adopted. The results show that as the overall density increases, the atomic density profiles of water inside CNTs become sharper, the peaks shift closer to the wall, and a new peak of hydrogen atomic density appears between the first (outermost) and second layer. The intermittent hydrogen bond correlation function C(HB)(t) of water inside CNTs decays slower than that of bulk water, and the rate of decay decreases as the tube diameter decreases. C(HB)(t) clearly decays more slowly for the first layer of water than for other regions inside CNTs. The C(HB)(t) of the interlayer hydrogen bonds decays faster than those of the other regions and even faster than that of the bulk water. On the other hand, the hydrogen bond lifetimes of the first layer are shorter than those of the inner layer(s). Interlayer hydrogen bond lifetimes are clearly shorter than those of the constituent layers. As a whole, the hydrogen bond lifetimes of water inside CNTs are shorter than those of bulk water, while the relaxation of C(HB)(t) is slower for the confined water than for bulk water. In other words, hydrogen bonds of water inside CNTs break more easily than those of bulk water, but the water molecules remain in each other's vicinity and can easily reform the bonds.     

Secondary structure sensitivity of hydrogen bond lifetime dynamics in the protein hydration layer

The heterogeneous nature of a protein surface plays an essential role in its biological activity and molecular recognition, and this role is mediated at least partly through the surrounding water molecules. We have performed atomistic molecular dynamics simulations of an aqueous solution of HP-36 to investigate the correlation between the dynamics of the hydration layer water molecules and the lifetimes of protein-water hydrogen bonds. The nonexponential hydrogen bond lifetime correlation functions have been analyzed by using the formalism of Luzar and Chandler, which allowed identification of the quasi-bound states in the surface and quantification of the dynamic equilibrium between quasi-bound and free water molecules in terms of time-dependent rate of interconversion. It is noticed that, irrespective of the structural heterogeneity of different segments of the protein, namely the three alpha-helices, the positively charged amino acid residues form longer-lived hydrogen bonds with water. The overall relaxation behavior of protein-water hydrogen bonds is found to differ significantly among the three helices of the protein. Study of water number density fluctuation reveals that the hydration layer of helix-3 is much less rigid, which can be correlated with faster structural relaxation of the hydrogen bonds between its residues and water. This also agrees excellently with faster translational and rotational motions of water near helix-3, and hence the lower rigidity of its hydration layer. The lower rigidity of the helix-3 hydration layer also correlates well with the biological activity of the protein, as several of the active-site residues of HP-36 are located in helix-3.     

水溶液中氢键寿命的定义和弛豫机理

氢键弛豫过程决定水溶液中分子的动力学行为,氢键寿命作为理论和实验结果中一个重要的参数通常用以描述溶液中的氢键动力学性质.本文采用SPC/E-P2和SPC/E-OPLS两种力场方法对二甲基亚砜(DMSO)水溶液体系进行分子动力学模拟,计算了四种不同定义下的氢键寿命,并进行了对比阐述,连续性氢键寿命Tc和基于动力学平衡方法下的氢键寿命TR较短,它们忽略了不成功的氢键交换过程,稳定态模型下的氢键寿命TPR能够真实体现氧键转换过程,可作为标度衡量其它量值.间歇性氢键寿命T相对最长,重复统计了氢键成功交换后的恢复概率.随着二甲基亚砜浓度增大,TC、TI、TR和TPR不断增大,分子平动扩散系数在中等浓度达到极小,说明氢键寿命与分子活动性无决定性关联,同类型氢键在不同浓度下的寿命差异表明氢键寿命具有分子环境依赖性;水分子和二甲基亚砜分子氢键个数降低,氢键受激角度扭曲和拉伸概率下降,TC和TR不断接近,氢键交换受体密度降低使氢键交换速率下降,TPR不断增大,氢键寿命与其周围氢键密度密切相关.TI与TPR的比值体现了氢键交换的局域性,其变化趋势与分子平动活动性趋势相同.两种力场下氢键寿命的差异也说明氢键的寿命具有明显的理论模型依赖性.