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Pore-forming toxins are an important component of the venom of many animals. Actinoporins are potent cytolysins that were first detected in the venom of sea anemones; however, they are occasionally found in animals other than cnidarians and are expanded in a few predatory gastropods. Here, we report the presence of 27 unique actinoporin-like genes with monophyletic origin in Mytilus galloprovincialis, which we have termed mytiporins. These mytiporins exhibited a remarkable level of molecular diversity and gene presence–absence variation, which warranted further studies aimed at elucidating their functional role. We structurally and functionally characterized mytiporin-1 and found significant differences from the archetypal actinoporin fragaceatoxin C. Mytiporin-1 showed weaker permeabilization activity, no specificity towards sphingomyelin, and weak activity in model lipid systems with negatively charged lipids. In contrast to fragaceatoxin C, which forms octameric pores, functional mytiporin-1 pores on negatively charged lipid membranes were hexameric. Similar hexameric pores were observed for coluporin-26 from Cumia reticulata and a conoporin from Conus andremenezi. This indicates that also other molluscan actinoporin-like proteins differ from fragaceatoxin C. Although the functional role of mytiporins in the context of molluscan physiology remains to be elucidated, the lineage-specific gene family expansion event that characterizes mytiporins indicates that strong selective forces acted on their molecular diversification. Given the tissue distribution of mytiporins, this process may have broadened the taxonomic breadth of their biological targets, which would have important implications for digestive processes or mucosal immunity.

Graphical abstract, Highlights • High-resolution solution NMR structure of rhNGF has been determined. • Quinary interactions characterize ATP binding to rhNGF. • SPR, ITC and STD-NMR reveal ATP binding to rhNGF with mM affinity. • NMR and MD analysis pinpoint to the presence of two binding sites of ATP on rhNGF. • Stoichiometry of ATP-Mg2+ or Zn2+-rhNGF mixtures affects KD affinity to TrkA/p75NTR., The Nerve Growth Factor (NGF) neurotrophin acts in the maintenance and growth of neuronal populations. Despite the detailed knowledge of NGF’s role in neuron physiology, the structural and mechanistic determinants of NGF bioactivity modulated by essential endogenous ligands are still lacking. We present the results of an integrated structural and advanced computational approach to characterize the extracellular ATP-NGF interaction. We mapped by NMR the interacting surface and ATP orientation on NGF and revealed the functional role of this interaction in the binding to TrkA and p75NTR receptors by SPR. The role of divalent ions was explored in conjunction with ATP. Our results pinpoint ATP as a likely transient molecular modulator of NGF signaling, in health and disease states.

The KV10.1 voltage-gated potassium channel is highly expressed in 70% of tumors, and thus represents a promising target for anticancer drug discovery. However, only a few ligands are known to inhibit KV10.1, and almost all also inhibit the very similar cardiac hERG channel, which can lead to undesirable side-effects. In the absence of the structure of the KV10.1–inhibitor complex, there remains the need for new strategies to identify selective KV10.1 inhibitors and to understand the binding modes of the known KV10.1 inhibitors. To investigate these binding modes in the central cavity of KV10.1, a unique approach was used that allows derivation and analysis of ligand–protein interactions from molecular dynamics trajectories through pharmacophore modeling. The final molecular dynamics-derived structure-based pharmacophore model for the simulated KV10.1–ligand complexes describes the necessary pharmacophore features for KV10.1 inhibition and is highly similar to the previously reported ligand-based hERG pharmacophore model used to explain the nonselectivity of KV10.1 pore blockers. Moreover, analysis of the molecular dynamics trajectories revealed disruption of the π–π network of aromatic residues F359, Y464, and F468 of KV10.1, which has been reported to be important for binding of various ligands for both KV10.1 and hERG channels. These data indicate that targeting the KV10.1 channel pore is also likely to result in undesired hERG inhibition, and other potential binding sites should be explored to develop true KV10.1-selective inhibitors as new anticancer agents.

Tower-technology-based concentrated solar power (CSP) promises to deliver electricity prices below 7.3 ¢ per kW h based on thermal energy storage and future renewable-energy harvesting technology. However, the price depends very much on the energy-transformation efficiency. Previous work on absorber coatings showed a reduced absorber efficiency over time. However, due to the extreme thermal and environmental loads during CSP operation, premature failure is expected. The absorber coating's service life, reflected in the energy-transformation efficiency vs. the operating time, is proportional to the profit expected by investors. In this study, using experimental testing combined with advanced analytics and theoretical modelling, we revealed that the field-equivalent thermal loads under isothermal and cyclic conditions facilitates the substrate oxidation. Most importantly, a state-of-the-art industrial coating composed of a black spinel pigment embedded in a silica matrix can serve for more than 10 years with a solar absorptance above 95%. Using advanced material characterization, providing detailed insights into the long-term stability and degradation mechanism under simulated operating conditions, we established the relationship between the coating's performance and its lifetime prediction.

The interaction between water and biomacromolecules is of fundamental interest in biophysics, biochemistry and physical chemistry. By combining neutron scattering and molecular dynamics simulations on a perdeuterated protein at a series of hydration levels, we demonstrated that the translational motion of water is slowed down more significantly than its rotation, when water molecules approach the protein molecule. Further analysis of the simulation trajectories reveals that the observed decoupling results from the fact that the translational motion of water is more correlated over space and more retarded by the charged/polar residues and spatial confinement on the protein surface, than the rotation. Moreover, around the stable protein residues (with smaller atomic fluctuations), water exhibits more decoupled dynamics, indicating a connection between the observed translation–rotation decoupling in hydration water and the local stability of the protein molecule.

Molecular solutes are known to have a strong effect on the structural and dynamical properties of the surrounding water. In our recent study (PNAS, 114, 322 (2017)) we have identified the presence of strengthened water hydrogen bonds near hydrophobic solutes by using both IR spectroscopy and ab-initio molecular dynamics simulations. The water molecules involved in the enhanced hydrogen bonding have been shown to display extensive structural ordering and restricted mobility. We observed that an individual pair of water molecules can make stronger hydrogen bond to each other if it is not surrounded by intercalating water molecules. Here we present compelling simulation results which unravel a simple mechanistic picture of the emergence of the hydrogen bond (HB) strengthening around solvated methane. We show explicitly that actual absence of water molecules within the excluded volume due to the hydrophobic molecule assures smaller residual torque on neighboring water molecules enabling the formation of stronger HBs between them.

Structural and functional studies of the coat protein regions of potato virus Y reveal crucial roles in viral infectivity., Potato virus Y (PVY) is among the most economically important plant pathogens. Using cryoelectron microscopy, we determined the near-atomic structure of PVY’s flexuous virions, revealing a previously unknown lumenal interplay between extended carboxyl-terminal regions of the coat protein units and viral RNA. RNA–coat protein interactions are crucial for the helical configuration and stability of the virion, as revealed by the unique near-atomic structure of RNA-free virus-like particles. The structures offer the first evidence for plasticity of the coat protein’s amino- and carboxyl-terminal regions. Together with mutational analysis and in planta experiments, we show their crucial role in PVY infectivity and explain the ability of the coat protein to perform multiple biological tasks. Moreover, the high modularity of PVY virus-like particles suggests their potential as a new molecular scaffold for nanobiotechnological applications.

Hydrophobicity plays an important role in numerous physicochemical processes from the process of dissolution in water to protein folding, but its origin at the fundamental level is still unclear. The classical view of hydrophobic hydration is that, in the presence of a hydrophobic solute, water forms transient microscopic "icebergs" arising from strengthened water hydrogen bonding, but there is no experimental evidence for enhanced hydrogen bonding and/or icebergs in such solutions. Here, we have used the redshifts and line shapes of the isotopically decoupled IR oxygen-deuterium (O-D) stretching mode of HDO water near small purely hydrophobic solutes (methane, ethane, krypton, and xenon) to study hydrophobicity at the most fundamental level. We present unequivocal and model-free experimental proof for the presence of strengthened water hydrogen bonds near four hydrophobic solutes, matching those in ice and clathrates. The water molecules involved in the enhanced hydrogen bonds display extensive structural ordering resembling that in clathrates. The number of ice-like hydrogen bonds is 10-15 per methane molecule. Ab initio molecular dynamics simulations have confirmed that water molecules in the vicinity of methane form stronger, more numerous, and more tetrahedrally oriented hydrogen bonds than those in bulk water and that their mobility is restricted. We show the absence of intercalating water molecules that cause the electrostatic screening (shielding) of hydrogen bonds in bulk water as the critical element for the enhanced hydrogen bonding around a hydrophobic solute. Our results confirm the classical view of hydrophobic hydration.

During drug development, it is important to have a suitable crystalline form of the active pharmaceutical ingredient (API). Mostly, the basic options originate in the form of free base, acid, or salt. Substances that are stable only within a certain pH range are a challenge for the formulation. For the prazoles, which are known to be sensitive to degradation in an acid environment, the formulation is stabilized with alkaline additives or with the application of API formulated as basic salts. Therefore, preparation and characterization of basic salts are needed to monitor any possible salinization of free molecules. We synthesized salts of omeprazole from the group of alkali metals (Li, Na, and K) and alkaline earth metals (Mg, Ca). The purpose of the presented work is to demonstrate the applicability of vibrational spectroscopy to discriminate between the OMP and OMP-salt molecules. For this reason, the physicochemical properties of 5 salts were probed using infrared and Raman spectroscopy, NMR, TG, DSC, and theoretical calculation of vibrational frequencies. We found out that vibrational spectroscopy serves as an applicable spectroscopic tool which enables an accurate, quick, and nondestructive way to determine the characteristic of OMP and its salts.

The dissolution of the antihypertensive AT1 antagonist olmesartan in methanol generates in situ a new highly bioactive methyl ether analogue via S N 1 mechanism involving an intramolecular proton transfer from carboxyl to hydroxyl group. Theoretical calculations confirmed the thermodynamic control preference of methyl ether versus the antagonistic product methyl ester. Α facile synthetic method for olmesartan methyl ether from olmesartan or olmesartan medoxomil is also described. Interestingly, the introduction of the methyl group to olmesartan did not alter its pharmacological properties. This observation opens new avenues in the synthesis of novel drugs, since hydroxyl and carboxylate groups have an orthogonal relationship in many drugs.

Mycobacteria harbor unique proteins that regulate protein lysine acylation in a cAMP-regulated manner. These lysine acyltransferases from Mycobacterium smegmatis (KATms) and Mycobacterium tuberculosis (KATmt) show distinctive biochemical properties in terms of cAMP binding affinity to the N-terminal cyclic nucleotide binding domain and allosteric activation of the C-terminal acyltransferase domain. Here we provide evidence for structural features in KATms that account for high affinity cAMP binding and elevated acyltransferase activity in the absence of cAMP. Structure-guided mutational analysis converted KATms from a cAMP-regulated to a cAMP-dependent acyltransferase and identified a unique asparagine residue in the acyltransferase domain of KATms that assists in the enzymatic reaction in the absence of a highly conserved glutamate residue seen in Gcn5-related N-acetyltransferase-like acyltransferases. Thus, we have identified mechanisms by which properties of similar proteins have diverged in two species of mycobacteria by modifications in amino acid sequence, which can dramatically alter the abundance of conformational states adopted by a protein.

The conformational preferences of blocked alanine dipeptide (ADP), Ac-Ala-NHMe, in aqueous solution were studied using vibrational circular dichroism (VCD) together with density functional theory (DFT) calculations. DFT calculations of three most representative conformations of ADP surrounded by six explicit water molecules immersed in a dielectric continuum have proven high sensitivity of amide III VCD band shape that is characteristic for each conformation of the peptide backbone. The polyproline II (PII) and αR conformation of ADP are associated with a positive VCD band while β conformation has a negative VCD band in amide III region. Knowing this spectral characteristic of each conformation allows us to assign the experimental amide III VCD spectrum of ADP. Moreover, the amide III region of the VCD spectrum was used to determine the relative populations of conformations of ADP in water. Based on the interpretation of the amide III region of VCD spectrum we have shown that dominant conformation of ADP in water is PII which is stabilized by hydrogen bonded water molecules between CO and NH groups on the peptide backbone. © 2014 Wiley Periodicals, Inc. Biopolymers 101: 814–818, 2014.

Recent guidelines for the third generation of solar absorber coatings have shown an unavoidable necessity for low thermal emittance coatings for concentrated solar power tower technology to decrease the thermal loss at the absorber surface. By tuning the pigment spinel crystal structure, density or roughness of a coating, improved optical properties for the coating can be achieved. In this study, a high solar-radiation absorbing pigment CuMn1.5Fe0.5O4 was calcined with 3 wt % Al, Fe, Ni, Mo and Cr to study the optical property improvement of the absorber coating, which could increase the efficiency of concentrated solar power plants. The modified pigment particles were investigated and compared to the non-modified pigment by XRD, TEM and elemental mapping, which showed that the pigment was successfully doped with Fe, Ni, and Cr. In contrast, no spinel doping was observed when Al and Mo were used. The most likely final position of the migrating Cr atoms was determined by comparing the experimental IR spectrum of the Cr-doped spinel structure with the spectra of various structures calculated based on first principles density functional theory calculations. Furthermore, the prepared coatings were thermally aged for 1300 h at 800 °C in air, followed by repetitive optical measurements. Outstanding results were achieved for the aged coating, which was made from a Cr-doped black pigment. Its solar absorptance (>95%) and eT/αS ratio (0.94) after 1300 h of thermal ageing were better than that of a standard paint (eT/αS = 1). We estimated that it may be possible to save up to 300,000 €/year on a fully operating concentrated solar power (CSP) plant by replacing the standard absorber paint with the Cr-doped pigment due to its better absorption efficiency.

Neutron scattering experiments have demonstrated that binding of the cancer drug methotrexate softens the low-frequency vibrations of its target protein, dihydrofolate reductase (DHFR). Here, this softening is fully reproduced using atomic detail normal-mode analysis. Decomposition of the vibrational density of states demonstrates that the largest contributions arise from structural elements of DHFR critical to stability and function. Mode-projection analysis reveals an increase of the breathing-like character of the affected vibrational modes consistent with the experimentally observed increased adiabatic compressibility of the protein on complexation.

Previous experimental studies have demonstrated changing the ionic strength of the solvent to have a great impact on the mechanism of aggregation of amyloid-beta (Aβ) protein leading to distinct fibril morphology at high and low ionic strength. Here, we use molecular dynamics simulations to elucidate the ionic strength-dependent effects on the structure and dynamics of the model Aβ fibril. The change in ionic strength was brought forth by varying the NaCl concentration in the environment surrounding the Aβ fibril. Comparison of the calculated vibrational spectra of Aβ derived from 40 ns all-atom molecular dynamics simulations at different ionic strength reveals the fibril structure to be stiffer with increasing ionic strength. This finding is further corroborated by the calculation of the stretching force constants. Decomposition of binding and dynamical properties into contributions from different structural segments indicates the elongation of the fibril at low ionic strength is most likely promoted by hydrogen bonding between N-terminal parts of the fibril, whereas aggregation at higher ionic strength is suggested to be driven by the hydrophobic interaction.

Collagen is a fibrous protein, which exists widely in the human body. The biomechanical properties of collagen depend on its triple helix structure and the corresponding low frequency vibrations. We use first-principles, density functional theory methods and analytical force fields to investigate the molecular vibrations of a model collagen compound, the results being validated by comparison with published, inelastic neutron scattering data. The results from these atomistic simulations are used at higher frequency to study the Amide I and V vibrations and therefore the vibrational signature of secondary and tertiary structure formation. In addition to collagen, its component homopolymers, poly-glycine and poly-proline are also studied. The Amide V vibration of glycine is strongly modified in going from the single helix of poly-glycine II to the triple helix of collagen. The collagen models are hydrated and this work allows us to discuss the relative merits of density functional theory and force field methods when tackling complex, partially crystalline systems.

A novel dinuclear complex [Cu2(μ-L)4(HL)2] (1) was isolated from starting 2-pyridone (HL) via a resonance and a tautomeric transformation. Each copper centre is in a square-pyramidal coordination sphere, defined by two oxygen atoms (Cu–O4 1.978(5), Cu–O11 1.964(4) A) and two nitrogen atoms (Cu–N2 2.003(5), Cu–N3 2.007(5) A) of four bridging deprotonated pyridin-2-olates and an oxygen atom on the top from a neutral 2-pyridone (Cu–O2 2.227(5) A), analogous to tetracarboxylate paddle-wheel complexes. Compound 1 was compared with mixed pyridin-2-olato/methanoato analogues [Cu2(μ-HCO2)2(μ-L)2(HL)2] · 2CH3CN (2) and [Cu2(μ-HCO2)2(μ-L)2(HL)2] (2a) (2a is an air stable form obtained from 2 outside mother-liquid). The EPR spectra of air stable 1 and 2a show three signals Hz1, H⊥2 and Hz2, typical for the binuclear systems with spin S = 1, both revealing strong antiferromagnetism 2J = −334 (1) and −324 cm−1 (2a). Interestingly, only for 1 additional H⊥1 signal at 100 mT is noticed (D(1) = 0.293 cm−1

Computational tools for normal mode analysis, which are widely used in physics and materials science problems, are designed here in a single package called NMscatt (Normal Modes & scattering) that allows arbitrarily large systems to be handled. The package allows inelastic neutron and X-ray scattering observables to be calculated, allowing comparison with experimental data produced at large scale facilities. Various simplification schemes are presented for analysing displacement vectors, which are otherwise too complicated to understand in very large systems., 13 pages, 5 figures, preprint submitted to Computer Physics Communications

The apparent simplicity of the water molecule belies the wide range of fascinating protein phenomena in which it participates. We review recent computer simulation work on buried, internal water molecules, discussing the thermodynamics of water molecule binding and the participation of water in proton transfer reactions. Surface water molecules are also considered, with emphasis on the modification of average solvent structure on a protein surface, the role of water in the protein dynamical ‘glass’ transition and a simplified description of the protein motions thereby activated.

A method for the calculation of the electronic structure of molecules is presented that is based on the Kohn–Sham formulation of density functional theory. The method avoids calculating global molecular orbitals; therefore, the electron density is defined by means of numerically calculated one-electron Green's functions. The method adopts a strategy of dividing a molecule into atomic subsystems whereby the favorable linear scaling of computational costs is obtained. Formulating the electronic structure problem by means of Green's functions allows the introduction of an additional coupling between subsystems that is not present in familiar methods. Although the method is general and can be applied to molecules with an arbitrary structure, it is at present tested only on some linear molecules. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004

Background Cyclodextrins (CDs) in combination with therapeutic proteins and other bioactive compounds have been proposed as candidates that show enhanced chemical and enzymatic stability, better absorption, slower plasma clearance and improved dose–response curves or immunogenicity. As a result, an important number of therapeutic complexes between cyclodextrins and bioactive compounds capable to control several diseases have been developed. Results In this article, the synthesis and the structural study of a conjugate between a luteinizing hormone-releasing hormone (LHRH) analogue, related to the treatment of hormone dependent cancer and fertility, and modified β -cyclodextrin residue are presented. The results show that both the phenyl group of tyrosine (Tyr) as well as the indole group of tryptophan (Trp) can be encapsulated inside the cyclodextrin cavity. Solution NMR experiments provide evidence that these interactions take place intramolecularly and not intermolecularly. Conclusions The study of a LHRH analogue conjugated with modified β -cyclodextrin via high field NMR and MD experiments revealed the existence of intramolecular interactions that could lead to an improved drug delivery. General significance NMR in combination with MD simulation is of great value for a successful rational design of peptide–cyclodextrin conjugates showing stability against enzymatic proteolysis and a better pharmacological profile.

The conformational preferences of blocked alanine dipeptide (ADP), Ac-Ala-NHMe, in aqueous solution were studied using vibrational circular dichroism (VCD) together with density functional theory (DFT) calculations. DFT calculations of three most representative conformations of ADP surrounded by six explicit water molecules immersed in a dielectric continuum have proven high sensitivity of amide III VCD band shape that is characteristic for each conformation of the peptide backbone. The polyproline II (PII ) and αR conformation of ADP are associated with a positive VCD band while β conformation has a negative VCD band in amide III region. Knowing this spectral characteristic of each conformation allows us to assign the experimental amide III VCD spectrum of ADP. Moreover, the amide III region of the VCD spectrum was used to determine the relative populations of conformations of ADP in water. Based on the interpretation of the amide III region of VCD spectrum we have shown that dominant conformation of ADP in water is PII which is stabilized by hydrogen bonded water molecules between CO and NH groups on the peptide backbone.

Background In the present study, we show the correlation of quantum chemical structural descriptors with the activation barriers of the Diels-Alder ligations. A set of 72 non-catalysed Diels-Alder reactions were subjected to quantitative structure-activation barrier relationship (QSABR) under the framework of theoretical quantum chemical descriptors calculated solely from the structures of diene and dienophile reactants. Experimental activation barrier data were obtained from literature. Descriptors were computed using Hartree-Fock theory using 6-31G(d) basis set as implemented in Gaussian 09 software. Results Variable selection and model development were carried out by stepwise multiple linear regression methodology. Predictive performance of the quantitative structure-activation barrier relationship (QSABR) model was assessed by training and test set concept and by calculating leave-one-out cross-validated Q2 and predictive R2 values. The QSABR model can explain and predict 86.5% and 80% of the variances, respectively, in the activation energy barrier training data. Alternatively, a neural network model based on back propagation of errors was developed to assess the nonlinearity of the sought correlations between theoretical descriptors and experimental reaction barriers. Conclusions A reasonable predictability for the activation barrier of the test set reactions was obtained, which enabled an exploration and interpretation of the significant variables responsible for Diels-Alder interaction between dienes and dienophiles. Thus, studies in the direction of QSABR modelling that provide efficient and fast prediction of activation barriers of the Diels-Alder reactions turn out to be a meaningful alternative to transition state theory based computation.

DNA melts at temperatures around 70 °C (~340 K) depending on the base-pair composition, level of hydration, type of counterions and excess salt concentration. Vibrational modes, which increase the separation between base molecules, i.e. perform the base pair opening, are thought to play an important role in DNA-bubble formation but these are typically assigned frequencies around 90 cm-1 (120 K). Understanding DNA melting and related biological processes requires this apparent energy gap of more than 200 K to be understood. We have performed atomistic molecular simulations which enable us to reconcile this energy difference between cause and effect. Using quasi-harmonic analysis we have analyzed the way in which vibrational modes of DNA change with the temperature.

We investigated the housekeeping cytochrome P450 CYP51A1 encoding lanosterol 14α-demethylase from cholesterol synthesis that was so far not directly linked to human disorders. By direct sequencing of CYP51A1 in 188 women with spontaneous preterm delivery and 188 unrelated preterm infants (gestational age

Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, M407 Walters Life Sciences,1414 Cumberland Avenue, Knoxville, Tennessee 37996, USA(Received 21 February 2013; revised manuscript received 2 August 2013; published 18 September 2013)Theinteractionbetweentwoassociatinghydrophobicparticleshastraditionallybeenexplainedintermsof the release of entropically frustrated hydration shell water molecules. However, this picture cannotaccount for the kinetics of hydrophobic association and is therefore not capable of providing a micro-scopic description of the hydrophobic interaction (HI). Here, Monte Carlo simulations of a pair ofmolecular-scale apolar solutes in aqueous solution reveal the critical role of collective fluctuations in thehydrogen bond (HB) network for the microscopic picture of the HI. The main contribution to the HI isthe relaxation of solute-water translational correlations. The existence of a heat capacity maximum at thedesolvation barrier is shown to arise from softening of non-HB water fluctuations and the relaxation ofmany-body correlations in the labile HB network. The microscopic event governing the kinetics ofhydrophobic association has turned out to be a relatively large critical collective fluctuation in hydrationwater displacing a substantial fraction of HB clusters from the inner to the outer region of the firsthydration shell.

A method based on density functional theory which utilizes the numerical calculation of one-electron Green's function instead of the diagonalization of the Kohn-Sham Hamiltonian is presented. The method is applied to atoms employing the approximation of spherically averaged electron density. The use of rectangular non-uniformly spaced basis functions for the representation of the radial part of the Hamiltonian provides a favourable dependence of the results on numerical parameters and a simple implementation scheme with the computational cost scaling linearly with the number of electrons. The all-electron SCF calculation within the generalized gradient approximation leads to encouraging results for the total and first ionization energies.

The hydrophobic effect (HE) is commonly associated with the demixing of oil and water at ambient conditions and plays the leading role in determining the structure and stability of biomolecular assembly in aqueous solutions. On the molecular scale HE has an entropic origin. It is believed that hydrophobic particles induce order in the surrounding water by reducing the volume of configuration space available for hydrogen bonding. Here we show with computer simulation results that this traditional picture, based on average structural features of hydration water, configurational properties of single water molecules, and up to pairwise correlations, is not correct. Analyzing collective fluctuations in water clusters we are able to provide a fundamentally new picture of HE based on pronounced many-body correlations affecting the switching of hydrogen bonds (HBs) between molecules. These correlations emerge as a nonlocal compensation of reduced fluctuations of local electrostatic fields in the presence of an apolar solute. We propose an alternative view which may also be formulated as a maximization principle: The electrostatic noise acting on water molecules is maximized under the constraint that each water molecule on average maintains as many HBs as possible. In the presence of the solute the maximized electrostatic noise is a result of nonlocal fluctuations in the labile HB network giving rise to strong correlations among at least up to four water molecules.

Monte Carlo simulations of a small model solute in an aqueous solution are used to examine the effects of solute polarity on hydration structure. A judicious definition of the orientational order parameter leads to reinterpretation of the conventional picture of hydration. As the solute varies from hydrophobic to hydrophilic the ordered first shell water simultaneously fractionates into a more highly ordered and a more disordered component. The hydrogen-bond network rearranges such that the more ordered component relaxes to configurations of optimal intermolecular angles, the other fraction being released from the network.

Quantifying the molecular elasticity of DNA is fundamental to our understanding of its biological functions. Recently different groups, through experiments on tailored DNA samples and numerical models, have reported a range of stretching force constants (0.3 to 3 N=m). However, the most direct, microscopic measurement of DNA stiffness is obtained from the dispersion of its vibrations. A new neutron scattering spectrometer and aligned, wet spun samples have enabled such measurements, which provide the first data of collective excitations of DNA and yield a force constant of 83 N=m. Structural and dynamic order persists unchanged to within 15 K of the melting point of the sample, precluding the formation of bubbles. These findings are supported by large scale phonon and molecular dynamics calculations, which reconcile hard and soft force constants.