Comments on a model for isotope effects on Henry's law constants in aqueous solution

A model has been proposed in the literature for isotope effects on Henry's law constants in which the motion of the dissolved molecule surrounded by a solvent cage is approximated by the motion of a particle in a cubic box. The isotope effect then arises from the three free translations of the gas phase molecule which become the restricted translations of a particle in a box for the dissolved molecule. The theoretical equation for the isotope effect is derived here on the basis of this model. Zero-point energy arguments have been used in the literature in conjunction with this model to deduce solvent cage dimensions from observed isotope effect data. These arguments are shown here to be theoretically wrong. The correct theory for the particle in a box model gives much larger dimensions for the solvent cage than the incorrect zero-point energy argument.     

Prediction of hydrogen solubility in heavy hydrocarbons over a range of temperatures and pressures using molecular dynamics simulations

Using the method of molecular dynamics (MD), we have estimated the solubility of hydrogen in heavy hydrocarbons for a range of temperatures and pressures. Heavy hydrocarbon systems are known to be challenging not only for experimental measurements but also for reliable estimations using traditional equations of state (EOS). The simulation system used was designed with semi-permeable membranes to mimic actual experimental studies of gas solubility. Binary interaction parameters between the solute gas and the solvent (heavy hydrocarbons) components were adjusted when necessary to improve agreement with experimental results and then used in subsequent multi-component studies. Temperature and pressure ranges studied included higher temperatures and pressures which are especially difficult to investigate experimentally. Simulation results were finally used to adjust the binary interaction parameters (BIP) in simulation packages (e.g. Aspen) to enable quick and reliable predictions.     

Henry's constants of n-alkanols (methanol through n-hexanol) in water at temperatures between 40°C and 90°C

Henry's constants of n-alkanols (methanol to n-hexanol) in water were measured at temperatures between 40°C and 90°C using a recently developed headspace gas chromatographic technique. The data were in good agreement with literature data when available. The consistency of the data was verified by comparing calculated partial molar enthalpies with calorimetric values. The temperature dependence of dimensionless Henry's constants was fitted with the classical van't Hoff equation and an empirical correlation was established for the dimensionless Henry's constants as a function of temperature and number of carbon atoms in the n-alkanol.     

Determination of Henry's law constants for low volatile mixed halogenated anisoles using solid-phase microextraction

Trihalogenated anisoles (THAs) that have been identified at low concentration levels (ng L⁻¹) in drinking water are suspected of causing odor episodes, which are a frequent source of complaint by consumers. Henry's law constant (K_H) is an important parameter in controlling the diffusion of organic compounds from the water to the vapor-phase, so its evaluation is of significance in the study of odor events. In this paper, the K_H of a wide range of trihalogenated anisoles - in its dimensionless form K^′H - were calculated at two temperatures, 45 and 22 °C using equilibration partitioning in a closed system and headspace microextraction (EPICS-SPME). Two methodological approaches, Ramachandran and Dewulf, were used for the assessment of the Henry's law constant. Nevertheless, to apply these methods to THAs, a relatively narrow headspace/water volume ratio range (80/1-8/1) is required. At these conditions, a linearity (r²) using Ramachandran's theoretical relationship from 0.9276 to 0.9989 was obtained and the variability (R.S.D.%) when Dewulf's theoretical relationship was employed was lower than 20% (n = 5).     

Determining equilibrium constants for dimerization reactions from molecular dynamics simulations

With today's available computer power, free energy calculations from equilibrium molecular dynamics simulations "via counting" become feasible for an increasing number of reactions. An example is the dimerization reaction of transmembrane alpha-helices. If an extended simulation of the two helices covers sufficiently many dimerization and dissociation events, their binding free energy is readily derived from the fraction of time during which the two helices are observed in dimeric form. Exactly how the correct value for the free energy is to be calculated, however, is unclear, and indeed several different and contradictory approaches have been used. In particular, results obtained via Boltzmann statistics differ from those determined via the law of mass action. Here, we develop a theory that resolves this discrepancy. We show that for simulation systems containing two molecules, the dimerization free energy is given by a formula of the form ΔG ∝ ln(P(1) /P(0) ). Our theory is also applicable to high concentrations that typically have to be used in molecular dynamics simulations to keep the simulation system small, where the textbook dilute approximations fail. It also covers simulations with an arbitrary number of monomers and dimers and provides rigorous error estimates. Comparison with test simulations of a simple Lennard Jones system with various particle numbers as well as with reference free energy values obtained from radial distribution functions show full agreement for both binding free energies and dimerization statistics.     

On the behaviour of solutions of xenon in liquid cycloalkanes: Solubility of xenon in cyclopentane

The solubility of xenon in liquid cyclopentane has been studied experimentally and theoretically. Measurements of the solubility of xenon in liquid cyclopentane are reported as a function of temperature from 254.60 K to 313.66 K. The imprecision of the experimental data is less than 0.3%. The thermodynamic functions of solvation of xenon in cyclopentane, such as the standard Gibbs energy, enthalpy, entropy and heat capacity of solvation, have been calculated from the temperature dependence of Henry's law coefficients. The results provide further information about the differences between the xenon + cycloalkanes and the xenon + n-alkane interactions. In particular, interaction enthalpies between xenon and CH₂ groups in n-alkanes and cycloalkanes have been estimated and compared. Using a version of the soft-SAFT approach developed to model cyclic molecules, we were able to reproduce the experimental solubility for xenon in cyclopentane using simple Lorentz-Berthelot rules to describe the unlike interaction.     

Importance of the Debye interaction in organic solutions: Henry's law constants for polar liquids in nonpolar solvents and vice versa

Henry's law constants have been determined for -butyrolactone (BL), ethyl acetate (EA), and 2-methyl-3-pentanol (MEP) in mixtures of iso-octane (ISO) and toluene (TOL), for BL, EA, TOL, and ISO in cinnamaldehyde (CIN) and for TOL and ISO in each other and in BL. From these data and published vapor pressures, the activity coefficients at infinite dilution and the standard molar Gibbs free energy of transfer, G ₂ ⁰ of the solutes from dilute solution in ISO to dilute solution in each solvent medium have been calculated. The different behavior patterns of BL and EA are attributed to differences in their abilities to exist in different conformations possessing different dipole moments. For polar solutes, G ₂ ⁰ decreases with increasing polarizability of the solvent and with increasing dipole moment of the solute, suggesting increased contributions from dipole-induced dipole (Debye) interactions. The sigmoidal plot of G ₂ ⁰ against the change in pair potential energy calculated from the classical expressions suggests that G ₂ ⁰ seriously underestimates the strength of the Debye interactions in comparison with the London interactions.     

Coarse‐grained molecular dynamics simulations of protein–ligand binding

Coarse‐grained molecular dynamics (CGMD) simulations with the MARTINI force field were performed to reproduce the protein–ligand binding processes. We chose two protein–ligand systems, the levansucrase–sugar (glucose or sucrose), and LinB–1,2‐dichloroethane systems, as target systems that differ in terms of the size and shape of the ligand‐binding pocket and the physicochemical properties of the pocket and the ligand. Spatial distributions of the Coarse‐grained (CG) ligand molecules revealed potential ligand‐binding sites on the protein surfaces other than the real ligand‐binding sites. The ligands bound most strongly to the real ligand‐binding sites. The binding and unbinding rate constants obtained from the CGMD simulation of the levansucrase–sucrose system were approximately 10 times greater than the experimental values; this is mainly due to faster diffusion of the CG ligand in the CG water model. We could obtain dissociation constants close to the experimental values for both systems. Analysis of the ligand fluxes demonstrated that the CG ligand molecules entered the ligand‐binding pockets through specific pathways. The ligands tended to move through grooves on the protein surface. Thus, the CGMD simulations produced reasonable results for the two different systems overall and are useful for studying the protein–ligand binding processes. © 2014 Wiley Periodicals, Inc.     

Parameterization of electrostatic interactions for molecular dynamics simulations of heterocyclic polymers

The paper focuses on the problem of electrostatic interactions in molecular dynamics simulations of thermal properties of heterocyclic polymers. The study focuses on three thermoplastic polyimides synthesized on the basis of 1,3‐bis‐(3′,4‐dicarboxyphenoxy)benzene (dianhydride R) and three diamines: 4,4′‐bis‐(4″‐aminophenoxy) diphenylsulfone (diamine BAPS), 4,4′‐bis‐(4″‐aminophenoxy) biphenyl (diamine BAPB), and 4,4′‐bis‐(4''‐aminophenoxy) diphenyloxide (diamine BAPO). In the molecular dynamics simulations these polyimides were described by the Gromos53a5 force field. To parameterize the electrostatic interactions four methods of calculating the partial atomic charges were chosen: B3LYP/6–31G*(Mulliken), AM1(Mulliken), HF/6–31G*(Mulliken), and HF/6–31G*(ChelpG). As our parameterization is targeted to reproduce thermal properties of the thermoplastic polyimides, the choice of proper partial charges was finalized on a basis of the closest match between computational and experimental data for the thermal expansion coefficients of the polyimides below glass transition temperatures. Our finding clearly show that the best agreement with experimental data is achieved with the Mulliken partial atomic charges calculated by the Hartree‐Fock method with 6–31G* basis set. Furthermore, in addition to the thermal expansion coefficients this set of partial atomic charges predicts an experimentally observed relationship between glass transition temperatures of the three polyimides under study: . A mechanism behind the change in thermal properties upon the change in the chemical structure in considered polyimides may be related to an additional spatial ordering of sulfone groups due to dipole‐dipole interactions. Overall, the modified force‐field is proved to be suitable for accurate prediction of thermal properties of thermoplastic polyimides and can serve as a basis for building up atomistic theoretical models for describing other heterocyclic polymers in bulk. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 912–923     

Parameterization of peptide 13C carbonyl chemical shielding anisotropy in molecular dynamics simulations.

NMR chemical shielding anisotropy (CSA) relaxation is an important tool in the study of dynamical processes in proteins and nucleic acids in solution. Herein, we investigate how dynamical variations in local geometry affect the chemical shielding anisotropy relaxation of the carbonyl carbon nucleus, using the following protocol: 1) Using density functional theory, the carbonyl (13)C' CSA is computed for 103 conformations of the model peptide group N-methylacetamide (NMA). 2) The variations in computed (13)C' CSA parameters are fitted against quadratic hypersurfaces containing cross terms between the variables. 3) The predictive quality of the CSA hypersurfaces is validated by comparing the predicted and de novo calculated (13)C' CSAs for 20 molecular dynamics snapshots. 4) The CSA fluctuations and their autocorrelation and cross correlation functions due to bond-length and bond-angle distortions are predicted for a chemistry Harvard molecular mechanics (CHARMM) molecular dynamics trajectory of Ca(2+)-saturated calmodulin and GB3 from the hypersurfaces, as well as for a molecular dynamics (MD) simulation of an NMA trimer using a quantum mechanically correct forcefield. We find that the fluctuations can be represented by a 0.93 scaling factor of the CSA tensor for both R(1) and R(2) relaxations for residues in helix, coil, and sheet alike. This result is important, as it establishes that (13)C' relaxation is a valid tool for measurement of interesting dynamical events in proteins.     

Influence of electrostatic interactions on the properties of cyanobiphenyl liquid crystals predicted from atomistic molecular dynamics simulations

The influence of force field details in all-atom molecular dynamics (MD) simulations on the predicted thermodynamic, structural, and dynamic properties of bulk 4-cyano-4?-pentylbiphenyl (5CB) systems have been investigated in the 292–368 K temperature range. The effect of the molecular dipole moment and the details of dihedral potential for biphenyl unit were investigated using both polarisable (POL) and non-polarisable (NP) versions of the quantum chemistry-based force field. The predicted densities for the nematic and isotropic phases of bulk 5CB were found to be in excellent agreement with available experimental data. The nematic-isotropic transition temperature (T_NI) showed strong sensitivity to the force field details, MD simulations with partial atomic charge distributions and molecular dipole moment corresponding to high-level quantum chemistry calculations predicted an overestimation of the T_NI by about 30 K. Rescaling the charges to allow the molecular dipole to be closer to experimentally reported values of 5CB dipole in condensed phases, significantly improved the prediction of T_NI as well as other thermodynamic and dynamic properties of 5CB. We also discuss how the structural, thermodynamic, and dynamic properties of bulk 5CB are affected by the flexibility of the central biphenyl dihedral and the inclusion of induced polarisation effects.     

Prediction of retention data from stationary phase constants in gas chromatography

Summary Specific retention volumes and retention indices for selected compounds can be predicted from different sets of stationary phase constants by multiple regression. Errors in the corresponding calculated retention times are between 5 and 15%. Intercept (A) and slope (B) values are given for 72 McReynolds stationary phases. The A value can be predicted from the retention index of benzene with a standard deviation of 9%.     

The Henry's law constants of water in the binary mixtures of benzene,carbon tetrachloride,and cyclohexane at 25°C

The solubilities of water in each of the three binary mixtures benzene-carbon tetrachloride, benzene-cyclohexane, and carbon tetrachloride-cyclohexane were determined as a function of solvent composition at 25°C. It was found that, as with the pure solvents, water in the 0.50 mole fraction binary mixtures of these solvents obeyed Henry's law up to saturation. The experimentally determined solubilities were converted to Henry's law constants of water for the entire range of solvent compositions. These values for the Henry's law constants were compared with theoretically calculated values. The comparisons indicated that water in the benzene-cyclohexane and in the benzene-carbon tetrachloride mixtures was preferentially solvated by benzene. Preferential solvation of water was not indicated for the carbon tetrachloride-cyclohexane mixtures.     

Mixed monte carlo/molecular dynamics simulations in explicit solvent

A mixed Monte Carlo/Molecular Dynamics method using the trial moves for peptide backbone sampling known as Concerted Rotations with Angles was implemented. The algorithm was used to study polyalanine systems. Equivalent results to conventional Molecular Dynamics were obtained for simulations of Ala₆ in implicit solvent. To test the efficiency of the implemented method, several 150 ns simulations of Ala₁₂ in explicit water were performed. The results show that the present method yields significantly faster formation of secondary structure than the conventional Molecular Dynamics simulations. This opens the possibility to selectively sample alanine‐rich regions of larger peptides or proteins. It remains to be established whether hydrophilic amino acid residues can be successfully treated with the present methodology. © 2012 Wiley Periodicals, Inc.     

Dimer models for ErbB-2/neu transmembrane domains from molecular dynamics simulations

Interest in the transmembrane receptors tyrosine kinase of the erbB family is high due to the involvement of some of the members in human cancers. The original oncogenic alleles of neu discovered in rat neuroectodermal tumors lead to single Val664Glu substitution within the predicted transmembrane domain. Identical substitution at the homologous position 659 constitutively activates the oncogenic potential of the human ErbB-2 receptor by enhanced receptor dimer formation. The precise molecular details of receptor dimerization are still unknown and to acquire more knowledge of the mechanisms involved, molecular dynamics simulations are undertaken to study transmembrane dimer association. Transmembrane helices are predicted to associate in left-handed coiled-coil structures stabilized by Glu-Glu interhelix hydrogen bonds in the mutated form. The internal dynamics reveals π helix deformations which modify the helix-helix interface. Predicted models agree with those suggested from polarized IR and magic-angle spinning NMR spectroscopy. Received: 24 April 1998 / Accepted: 17 September 1998 / Published online: 10 December 1998     

Structure and dynamics of liquid water with different long-range interaction truncation and temperature control methods in molecular dynamics simulations

We have used molecular dynamics simulations to study the physical properties of modified TIP3P water model included in the CHARMM program, using four different methods-the Ewald summation technique, and three different spherical truncation methods-for the treatment of the long-range interactions. Both the structure and dynamics of the liquid water model were affected by the methods used to truncate the long-range interactions. For some of the methods artificial structuring of the model liquid was observed around the cutoff radius. The model liquid properties were also affected by the commonly applied temperature control methods. Four different methods for controlling the temperature of the system were studied, and the effects of these methods on the bulk properties for liquid water were analyzed. The system size was also found to change the dynamics of the model liquid water. Two control simulations with the SPC/E water model were carried out. The self-diffusion coefficient (D), the radial distribution function (g(OO)), the distance dependent Kirkwood G-factor [G(k)(r)] and the intermolecular potential energy (E(pot)) were determined from the different trajectories and compared with the experimental data.     

Mechanism of C-terminal intein cleavage in protein splicing from QM/MM molecular dynamics simulations

Protein splicing is a post-translational process in which a biologically inactive protein is activated by the release of a segment denoted as an intein. The process involves four steps. In the third, the scission of the intein takes place after the cyclization of the last amino acid of the segment, an asparagine. Little is known about the chemical reaction necessary for this cyclization. Experiments demonstrate that two histidines (the penultimate amino acid of the intein, and a histidine located 10 amino acids upstream) are relevant in the cyclization of the asparagine. We have investigated the mechanism and determinants of reaction in the GyrA intein focusing on the requirements for asparagine activation for its cyclization. First, the influence that the protonation states of these two histidines have on the orientation of the asparagine side chain is investigated by means of molecular dynamics simulation. Molecular dynamics simulations using the CHARMM27 force field were carried out on the three possible protonation states for each of these two histidines. The results indicate that the only protonation state in which the conformation of the system is suitable for cyclization is when the penultimate histidine is fully protonated (positively charged), and the upstream histidine is in the His(ε) neutral tautomeric form. The free energy profile for the reaction in which the asparagine is activated by a proton transfer to the upstream histidine is presented, computed by hybrid quantum mechanics/molecular mechanics (QM/MM) umbrella sampling molecular dynamics at the SCCDFTB/CHARMM27 level of theory. The calculated free energy barrier for the reaction is 19.0 kcal mol(-1). B3LYP/6-31+G(d) QM/MM single-point calculations give a qualitatively a similar energy profile, although with somewhat higher energy barriers, in good agreement with the value derived from experiment of 25 kcal mol(-1) at 60 °C. QM/MM molecular dynamics simulations of the reactant, activated reactant and intermediate states highlight the importance of the Arg181-Val182-Asp183 segment in catalysing the reaction. Overall, the results indicate that nucleophilic activation of the asparagine for its cyclization by the upstream histidine acting as the base is a plausible mechanism for the C-terminal cleavage in protein splicing.     

Insights into intrastrand cross-link lesions of DNA from QM/MM molecular dynamics simulations

DNA damages induced by oxidative intrastrand cross-links have been the subject of intense research during the past decade. Yet, the currently available experimental protocols used to isolate such lesions only allow to get structural information about linked dinucleotides. The detailed structure of the damaged DNA macromolecule has remained elusive. In this study we generated in silico the most frequent oxidative intrastrand cross-link adduct, G[8,5-Me]T, embedded in a solvated DNA dodecamer by means of quantum mechanics/molecular mechanics (QM/MM) Car-Parrinello simulations. The free energy of activation required to bring the reactant close together and to form the C-C covalent-bond is estimated to be ~10 kcal/mol. We observe that the G[8,5-Me]T tandem lesion is accommodated with almost no perturbation of the Watson-Crick hydrogen-bond network and induces bend and unwinding angles of ~20° and 8°, respectively. This rather small structural distortion of the DNA macromolecule compared to other well characterized intrastrand cross-links, such as cyclobutane pyrimidines dimers or cisplatin-DNA complex adduct, is a probable rationale for the known lack of efficient repair of oxidative damages.     

Modification of Guest and Saunders open shell SCF equations to exclude BSSE from molecular interaction calculations

The self-consistent field (SCF) for molecularinteractions algorithm, particularly devised to compute intermolecular interactions, is extended to the case in which one of the two interacting fragments is an open shell system. The method excludes the basis set superposition error in an a priori fashion. To preserve the simplicity of the standard SCF procedure, Guest and Saunders equations concerning the open shell fragment are modified at the cost of a negligible complication with respect to the usual algorithm. Received: 27 May 1997 / Accepted: 29 May 1998 / Published online: 18 September 1998