Computational study of the ground state of thermophilic indole glycerol phosphate synthase: structural alterations at the active site with temperature

Hyperthermophlic indole-3-glycerol phosphate synthase (IGPS) catalyzes the terminal ring-closure step in tryptophan biosynthesis. In this paper, we compare the results from the molecular dynamics (MD) simulation of enzyme-bound substrate at 298 K (E.S298) and 385 K (E.S385) solvated in the TIP3P water box using the CHARMM force field to address the question of the structural change of the Enzyme.Substrate complex with temperature. The population of the reactive Enzyme.Substrate conformers (near attack conformers or NACs) increases by approximately 1100-fold in going from room temperature (E.S298) to high temperature (E.S385). This increased population of NAC conformers in the Michaelis complex correlates well with the increase in rate in going from 298 to 385 K. The positioning of the two active site residues Lys53 and Lys110 controls binding of the substrate in the favorable orientation for general acid-catalyzed intramolecular ring formation reaction. It can be concluded that the NAC formation allowing general acid catalysis has much to do with the temperature dependence of the free energy of reaction.     

Phase diagram of water between hydrophobic surfaces

Molecular dynamics simulations demonstrate that there are at least two classes of quasi-two-dimensional solid water into which liquid water confined between hydrophobic surfaces freezes spontaneously and whose hydrogen-bond networks are as fully connected as those of bulk ice. One of them is the monolayer ice and the other is the bilayer solid which takes either a crystalline or an amorphous form. Here we present the phase transformations among liquid, bilayer amorphous (or crystalline) ice, and monolayer ice phases at various thermodynamic conditions, then determine curves of melting, freezing, and solid-solid structural change on the isostress planes where temperature and intersurface distance are variable, and finally we propose a phase diagram of the confined water in the temperature-pressure-distance space.     

Relation between solvent and protein dynamics as studied by dielectric spectroscopy

We present results obtained by dielectric spectroscopy in wide frequency (10(-2)-10(9) Hz) and temperature ranges on human hemoglobin in the three different solvents water, glycerol, and methanol, at a solvent level of 0.8 g of solvent/g of protein. In this broad frequency region, there are motions on several time-scales in the measured temperature range (110-370 K for water, 170-410 K for glycerol, and 110-310 K for methanol). For all samples, the dielectric data shows at least four relaxation processes, with frequency dependences that are well described by the Havriliak-Negami or Cole-Cole functions. The fastest and most pronounced process in the dielectric spectra of hemoglobin in glycerol and methanol solutions is similar to the alpha-relaxation of the corresponding bulk solvent (but shifted to slower dynamics due to surface interactions). For water solutions, however, this process corresponds to earlier results obtained for water confined in various systems and it is most likely due to a local beta-relaxation. The slowing down of the glycerol and methanol relaxations and the good agreement with earlier results on confined water show that this process is affected by the interaction with the protein surface. The second fastest process is attributed to motions of polar side groups on the protein, with a possible contribution from tightly bound solvent molecules. This process is shifted to slower dynamics with increasing solvent viscosity, and it shows a crossover in its temperature dependence from Arrhenius behavior at low temperatures to non-Arrhenius behavior at higher temperatures where there seems to be an onset of cooperativity effects. The origins of the two slowest relaxation processes (visible at high temperatures and low frequencies), which show saddlelike temperature dependences for the solvents water and methanol, are most likely due to motions of the polypeptide backbone and an even more global motion in the protein molecule.     

Glass transition in pure and doped amorphous solid water: an ultrafast microcalorimetry study

Using an ultrafast scanning microcalorimetry apparatus capable of heating rates in excess of 10(5) Ks, we have conducted the first direct measurements of thermodynamic properties of pure and doped amorphous solid water (also referred to as low density amorphous ice) in the temperature range from 120 to 230 K. Ultrafast microcalorimetry experiments show that the heat capacity of pure amorphous solid water (ASW) remains indistinguishable from that of crystalline ice during rapid heating up to a temperature of 205+/-5 K where the ASW undergoes rapid crystallization. Based on these observations, we conclude that the enthalpy relaxation time in pure ASW must be greater than 10(-5) s at 205 K. We argue that this result contradicts the assignment of glass transition temperature to 135 K and that ASW may undergo fragile to strong transition at temperatures greater than 205 K. Unlike pure ASW, we observe an approximately twofold rise in heat capacity of CH3COOH doped ASW at 177+/-5 K. We discuss results of past studies taking into account possible influence of impurities and confinement on physical properties of ASW.     

Study of the molecular motions of polyethylene by line-shape analysis of broad-line proton NMR spectra

The broad-line proton NMR spectra of polyethylene are separated into three components (broad, medium, and narrow) corresponding to the crystalline and two kinds of amorphous protons, respectively. All amorphous protons are found to be mobile above 210°K. The unusually low molecular mobility in the amorphous regions of polyethylene compared to purely amorphous and other partially crystalline polymers is considered to be adequately described by the network model of Edwards and De Gennes. In this model the chain motions are anisotropic and restricted to small tubular volumes. The medium and the narrow component are believed to result from two different modes of chain motion within these tubes, depending on the free volume available. Two motions in the crystalline regions are observed. One at temperatures below 110°K involves 2%–5% of the protons, depending on the crystallinity of the material, and the other beginning at 290°K involves all crystalline protons (α-process). Coupling of the amorphous and crystalline motions is found above 290°K. Several line shapes have been tested as representations of the three components. Of these the low-temperature spectrum, the Gauss–Lorentz product curve, and the Lorentz curve proved to be the most suitable shapes for the broad, medium, and narrow component, respectively. Using these line shapes, the best fit of the experimental spectra and the expected agreement of the broad and the crystalline fraction are obtained over a very broad temperature range. Above 310°K the low-temperature spectrum must be replaced by the convolution of a Gauss curve and a rectangular function to take into account the line-shape transition of the α-process. The modulation broadening of all components is considered, and this allows line-shape analysis close to the melting point.     

Molecular dynamics simulations of a poly(ethylene oxide) surface

Potentials developed earlier for crystalline and amorphous bulk PEO systems have been used for the MD simulation of a PEO surface model. The surface comprises the outer region of a 122 Å-thick sheet of PEO in which the PEO, -(CH₂-CH₂-O)_n- chains run obliquely across the cell, and are terminated by C₂H₅ ethyl groups. The atoms on one side of the sheet are tethered to facilitate a satisfactory Ewald summation. The sheet expands from its ‘crystalline’ width of 122 Å to 128 Å in the simulated model. Simulations were performed at three temperatures: 300 K, 400 K and 500 K. Different behaviour in the surface layer was found compared to that in the bulk. The structural and dynamical properties of the surface were analyzed at each temperature.     

Diffusion coefficients of small gas molecules in amorphous cis-1,4-polybutadiene estimated by molecular dynamics simulations

Molecular dynamics (MD) simulations were employed to estimate the diffusion coefficients of small gas molecules (Ar, O2, N2, CO2, and CH4) in amorphous cis-1,4-polybutadiene in the temperature range of 250-400 K. The VT diagram and solubility parameter of the amorphous polymer have been successfully reproduced using a full atomistic potential. Diffusion coefficients were calculated from long NPT MD runs (up to 3 ns) at temperature ranging from 250 up to 400 K. Calculated diffusion coefficients compare well with experimental data as well as previous published work, though a systematic overestimation is found due to the finite-size effect of the model. The influence of various physical and computational parameters on the results is discussed. The diffusion mechanism is examined at the different temperatures of study.     

Radiation effects in water ice: a near-edge x-ray absorption fine structure study

The changes in the structure and composition of vapor-deposited ice films irradiated at 20 K with soft x-ray photons (3-900 eV) and their subsequent evolution with temperatures between 20 and 150 K have been investigated by near-edge x-ray absorption fine structure spectroscopy (NEXAFS) at the oxygen K edge. We observe the hydroxyl OH, the atomic oxygen O, and the hydroperoxyl HO(2) radicals, as well as the oxygen O(2) and hydrogen peroxide H(2)O(2) molecules in irradiated porous amorphous solid water (p-ASW) and crystalline (I(cryst)) ice films. The evolution of their concentrations with the temperature indicates that HO(2), O(2), and H(2)O(2) result from a simple step reaction fuelled by OH, where O(2) is a product of HO(2) and HO(2) a product of H(2)O(2). The local order of ice is also modified, whatever the initial structure is. The crystalline ice I(cryst) becomes amorphous. The high-density amorphous phase (I(a)h) of ice is observed after irradiation of the p-ASW film, whose initial structure is the normal low-density form of the amorphous ice (I(a)l). The phase I(a)h is thus peculiar to irradiated ice and does not exist in the as-deposited ice films. A new "very high density" amorphous phase-we call I(a)vh-is obtained after warming at 50 K the irradiated p-ASW ice. This phase is stable up to 90 K and partially transforms into crystalline ice at 150 K.     

Temperature‐dependent changes in the hydrogen bonded hard segment network and microphase morphology in a model polyurethane: Experimental and simulation studies

Hydrogen bonding between hard segments has a critical effect on the morphology and properties of polyurethanes. Influence of temperature on hydrogen bonded urethane network and melting behavior of a model semicrystalline segmented polyurethane was investigated by experiments and simulations. Polyurethane was synthesized by the stoichiometric reaction between p‐phenylene diisocyanate and poly(tetramethylene oxide) (PTMO) with a molecular weight of 1000 g/mol. Simulations were carried out using dissipative particle dynamics (DPD) and molecular dynamics (MD) approaches. Experimental melting behavior obtained by various techniques was compared with simulations. DPD simulations showed a room temperature microphase morphology consisting of a three‐dimensional hydrogen‐bonded urethane hard segment network in a continuous and amorphous PTMO matrix. The first‐order melting transitions of crystalline urethane hard segments observed during the continuous isobaric heating in DPD and MD simulations (340–360 K) were in reasonably good agreement with those observed experimentally, such as AFM (320–340 K), WAXS (330–360 K), and FTIR (320–350 K) measurements. Quantitative verification of the melting of urethane hard segments was demonstrated by sharp discontinuities in energy versus temperature plots obtained by MD simulations due to substantial decrease in the number of hydrogen bonds above 340 K. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018 , 56, 182–192     

Convergence of folding free energy landscapes via application of enhanced sampling methods in a distributed computing environment

We have implemented the serial replica exchange method (SREM) and simulated tempering (ST) enhanced sampling algorithms in a global distributed computing environment. Here we examine the helix-coil transition of a 21 residue alpha-helical peptide in explicit solvent. For ST, we demonstrate the efficacy of a new method for determining initial weights allowing the system to perform a random walk in temperature space based on short trial simulations. These weights are updated throughout the production simulation by an adaptive weighting method. We give a detailed comparison of SREM, ST, as well as standard MD and find that SREM and ST give equivalent results in reasonable agreement with experimental data. In addition, we find that both enhanced sampling methods are much more efficient than standard MD simulations. The melting temperature of the Fs peptide with the AMBER99phi potential was calculated to be about 310 K, which is in reasonable agreement with the experimental value of 334 K. We also discuss other temperature dependent properties of the helix-coil transition. Although ST has certain advantages over SREM, both SREM and ST are shown to be powerful methods via distributed computing and will be applied extensively in future studies of complex bimolecular systems.     

Electronic structures and hydrogen bond network of high-density and very high-density amorphous ices

Electronic structures of hexagonal ice (ice Ih), high-density amorphous ice (HDA), and very high-density amorphous ice (VHDA) are investigated using ab initio density functional theory (DFT) at 77 K under a pressure of 0.1 MPa, focusing on band structure, density of states (DOS), partial density of states (PDOS), and electron density. It is found that the integration intensity of the O-2p bonding band in HDA is 1.53 eV wider than that in the VHDA. Because more 2p electrons in HDA participate the 2p-1s hybridization of O-H. The classical molecular dynamics (MD) method has further been carried out to analyze the hydrogen bond network of HDA and VHDA with larger numbers of water molecules under the same temperature, pressure, and boundary conditions used as those during the DFT calculation. MD results show that there exists some water molecules with five hydrogen bonds in both HDA (4.1 +/- 0.1%) and VHDA (2.8 +/- 0.1%), as compared with the LDA, being consistent with the integration intensity results of PDOS. This result can be used to interpret the physical nature of the similar transition temperature of HDA and VHDA to LDA with different heating rates.     

Direct observation of a transverse vibrational mechanism for negative thermal expansion in Zn(CN)2: an atomic pair distribution function analysis

The instantaneous structure of the cyanide-bridged negative thermal expansion (NTE) material Zn(CN)(2) has been probed using atomic pair distribution function (PDF) analysis of high energy X-ray scattering data (100-400 K). The temperature dependence of the atomic separations extracted from the PDFs indicates an increase of the average transverse displacement of the cyanide bridge from the line connecting the Zn(II) centers with increasing temperature. This allows the contraction of non-nearest-neighbor Zn...Zn' and Zn...C/N distances despite the observed expansion of the individual direct Zn-C/N and C-N bonds. Thus, this analysis provides definitive structural confirmation that an increase in the average displacement of bridging atoms is the origin of the NTE behavior. The lattice parameters reveal a slight reduction in the NTE behavior at high temperature from a minimum coefficient of thermal expansion (alpha = dl/ldT) of -19.8 x 10(-6) K(-1) below 180 K, which is attributed to interaction between the doubly interpenetrated frameworks that comprise the structure.     

The glass transition behaviors of low-density amorphous ice films with different thicknesses

The glass transition behaviors of amorphous ice with different thicknesses are studied by determining the heat capacity of low-density amorphous ice without crystallization using first principle molecular dynamics (FP-MD) and classical MD methods. The behaviors are also studied by analyzing hydrogen-bond network, the radial distribution functions, and relationship between hydrogen bond and electronic structures. It is found that the glass transition temperature (T(g)) in the range of 90 K < T < 100 K for 4 nm amorphous ice film by FP-MD method, and 120 K < T(g) < 130 K for 8 nm amorphous ice film by MD method. Meanwhile, T(g) decreases with the decreasing thickness of amorphous ice film, which is also validated by the theoretical model.     

Sticking of CO to crystalline and amorphous ice surfaces

We present results of classical trajectory calculations on the sticking of hyperthermal CO to the basal plane (0001) face of crystalline ice Ih and to the surface of amorphous ice Ia. The calculations were performed for normal incidence at a surface temperature Ts = 90 K for ice Ia, and at Ts = 90 and 150 K for ice Ih. For both surfaces, the sticking probability can be fitted to a simple exponentially decaying function of the incidence energy, Ei: Ps = 1.0e(-Ei(kJ/mol)/90(kJ/mol)) at Ts = 90 K. The energy transfer from the impinging molecule to the crystalline and the amorphous surface is found to be quite efficient, in agreement with the results of molecular beam experiments on the scattering of the similar molecule, N2, from crystalline and amorphous ice. However, the energy transfer is less efficient for amorphous than for crystalline ice. Our calculations predict that the sticking probability decreases with Ts for CO scattering from crystalline ice, as the energy transfer from the impinging molecule to the warmer surfaces becomes less efficient. At high Ei (up to 193 kJ/mol), no surface penetration occurs in the case of crystalline ice. However, for CO colliding with the amorphous surface, a penetrating trajectory was observed to occur into a large water pore. The molecular dynamics calculations predict that the average potential energy of CO adsorbed to ice Ih is -10.1 +/- 0.2 and -8.4 +/- 0.2 kJ/mol for CO adsorbed to ice Ia. These values are in agreement with previous experimental and theoretical data. The distribution of the potential energy of CO adsorbed to ice Ia was found to be wider (with a standard deviation sigma of 2.4 kJ/mol) than that of CO interacting with ice Ih (sigma = 2.0 kJ/mol). In collisions with ice Ia, the CO molecules scatter at larger angles and over a wider distribution of angles than in collisions with ice Ih.     

半晶PBT在室温存放时的聚态结构变化

用DSC观察了不同冷却条件半晶PBT样品在室温存放时所发生的聚态结构变化。实验表明,在310～325K出现的热焓松弛峰的峰高和峰温随存放时间的变化与冷却条件有关。该峰表征试样中“硬无定形部分”的松弛。本文定量地描述了它的峰高与峰温对存放时间的依赖关系。发现水对松弛过程和随之发生的冷结晶有一定程度的抑制。室温存放过程中,晶态结构缺陷有,所减少并少量新的亚稳态晶体形成。     

Redox entropy of plastocyanin: developing a microscopic view of mesoscopic polar solvation

We report applications of analytical formalisms and molecular dynamics (MD) simulations to the calculation of redox entropy of plastocyanin metalloprotein in aqueous solution. The goal of our analysis is to establish critical components of the theory required to describe polar solvation at the mesoscopic scale. The analytical techniques include a microscopic formalism based on structure factors of the solvent dipolar orientations and density and continuum dielectric theories. The microscopic theory employs the atomistic structure of the protein with force-field atomic charges and solvent structure factors obtained from separate MD simulations of the homogeneous solvent. The MD simulations provide linear response solvation free energies and reorganization energies of electron transfer in the temperature range of 280-310 K. We found that continuum models universally underestimate solvation entropies, and a more favorable agreement is reported between the microscopic calculations and MD simulations. The analysis of simulations also suggests that difficulties of extending standard formalisms to protein solvation are related to the inhomogeneous structure of the solvation shell at the protein-water interface combining islands of highly structured water around ionized residues along with partial dewetting of hydrophobic patches. Quantitative theories of electrostatic protein hydration need to incorporate realistic density profile of water at the protein-water interface.     

Steered molecular dynamics studies of the potential of mean force of a Na+ or K+ ion in a cyclic peptide nanotube

Potential of mean force (PMF) profiles of a single Na+ or K+ ion passing through a cyclic peptide nanotube, cyclo[-(D-Ala-Glu-D-Ala-Gln)2-], in water are calculated to provide insight into ion transport and to understand the conductance difference between these two ions. The PMF profiles are obtained by performing steered molecular dynamics (SMD) simulations that are based on the Jarzynski equality. The computed PMF profiles for both ions show barriers of around 2.4 kcal/mol at the channel entrances and exits and energy wells in the middle of the tube. The energy barriers, so-called dielectric energy barriers, arise due to the desolvation of water molecules when ions move across the nanotube, and the energy wells appear as a result of attractive interactions between the cations and negatively charged carbonyl oxygens on the backbone of the tube. We find more and deeper energy wells in the PMF profile for Na+ than for K+, which suggests that Na+ ions have a longer residence time inside the nanotube and that permeation of Na+ ions is reduced compared to K+ ions. Calculations of the radial distribution functions (RDF) between the ions and oxygens in the water molecules and in carbonyl groups on the tube and an investigation of the orientations of the carbonyl groups show that, in contrast with the dynamic carbonyl groups observed in the selectivity filter of the KcsA ion channel, the carbonyl groups in the cyclic peptide nanotube are relatively rigid, with only slight reorientation of the carbonyl groups as the cations pass through. The rigidity of the carbonyl groups in the cyclic peptide nanotube can be attributed to their role in hydrogen bonding, which is responsible for the tube structure. Comparison of the PMF profiles with the electrostatic energy profiles calculated from the Poisson-Boltzmann (PB) equation, a dielectric continuum model, reveals that the dielectric continuum model breaks down in the confined region within the tube that governs ion transport.     

Effect of Nanoscale Confinement on Freezing of Modified Water at Room Temperature and Ambient Pressure

Understanding the phase behavior of confined water is central to fields as diverse as heterogeneous catalysis, corrosion, nanofluidics, and to emerging energy technologies. Altering the state points (temperature, pressure, etc.) or introduction of a foreign surface can result in the phase transformation of water. At room temperature, ice nucleation is a very rare event and extremely high pressures in the GPa–TPa range are required to freeze water. Here, we perform computer experiments to artificially alter the balance between electrostatic and dispersion interactions between water molecules, and demonstrate nucleation and growth of ice at room temperature in a nanoconfined environment. Local perturbations in dispersive and electrostatic interactions near the surface are shown to provide the seed for nucleation (nucleation sites), which lead to room temperature liquid–solid phase transition of confined water. Crystallization of water occurs over several tens of nanometers and is shown to be independent of the nature of the substrate (hydrophilic oxide vs. hydrophobic graphene and crystalline oxide vs. amorphous diamond‐like carbon). Our results lead us to hypothesize that the freezing transition of confined water can be controlled by tuning the relative dispersive and electrostatic interaction.     

Local order and dynamics in supercooled water: a study by IR spectroscopy and molecular dynamic simulations

Micron-sized water droplets in a cryogenic flow tube were probed by IR spectroscopy. The analysis of the IR spectra suggests that there is a relative increase of about 30% in the fraction, f(L), of low density domains in water on cooling over the temperature range between 300 and 240 K. The results derived from the experiments agree qualitatively with those of molecular dynamics (MD) simulations in terms of the increase in the f(L) values. The MD simulations show that the intensities of the mode at about 100 cm(-1) for the molecules in the low density domains are reduced in comparison to the average, while the intensities and frequencies of the librational mode at 600 cm(-1) are increased. Furthermore, the reorientations (dielectric relaxation times) in these domains are found to be somewhat slower, pointing to the fact that these low density "cages" live longer than the average local molecular environments in supercooled water.     

Molecular-dynamics study of photodissociation of water in crystalline and amorphous ices

We present the results of classical dynamics calculations performed to study the photodissociation of water in crystalline and amorphous ice surfaces at a surface temperature of 10 K. A modified form of a recently developed potential model for the photodissociation of a water molecule in ice [S. Andersson et al., Chem. Phys. Lett. 408, 415 (2005)] is used. Dissociation in the top six monolayers is considered. Desorption of H(2)O has a low probability (less than 0.5% yield per absorbed photon) for both types of ice. The final outcome strongly depends on the original position of the photodissociated molecule. For molecules in the first bilayer of crystalline ice and the corresponding layers in amorphous ice, desorption of H atoms dominates. In the second bilayer H atom desorption, trapping of the H and OH fragments in the ice, and recombination of H and OH are of roughly equal importance. Deeper into the ice H atom desorption becomes less important and trapping and recombination dominate. Motion of the photofragments is somewhat more restricted in amorphous ice. The distribution of distances traveled by H atoms in the ice peaks at 6-7 Angstroms with a tail going to about 60 Angstroms for both types of ice. The mobility of OH radicals is low within the ice with most probable distances traveled of 2 and 1 Angstrom for crystalline and amorphous ices, respectively. OH is, however, quite mobile on top of the surface, where it has been found to travel more than 80 Angstroms. Simulated absorption spectra of crystalline ice, amorphous ice, and liquid water are found to be in very good agreement with the experiments. The outcomes of photodissociation in crystalline and amorphous ices are overall similar, but with some intriguing differences in detail. The probability of H atoms desorbing is 40% higher from amorphous than from crystalline ice and the kinetic-energy distribution of the H atoms is on average 30% hotter for amorphous ice. In contrast, the probability of desorption of OH radicals from crystalline ice is much higher than that from amorphous ice.