Direct observation of the substitution effects on the hydrogen bridge dynamics in selected Schiff bases--a comparative molecular dynamics study

We have studied substituent effects on the properties of the intramolecular hydrogen bond of some ortho-hydroxy Schiff bases using density functional theory (DFT) based first-principle molecular dynamics (FPMD) and path integral molecular dynamics. The studied compounds possess a strong intramolecular hydrogen bond (r((O???N)) ≤ 2.6 A?), which can be tuned by substitution to either (i) enhance the basicity of the acceptor moiety by induction effects or (ii) decrease the hydrogen bond length through steric repulsion. DFT calculations and FPMD were employed to investigate structural and dynamical properties of the selected molecules, while quantum effects on the structural properties were assessed using path integral FPMD. The simulations were performed in vacuo and in the solid state to study the influence of the environment on the hydrogen bond and spectroscopic properties. We give computational support to the suggestion that induction effects are less effective to tune the intramolecular hydrogen bond properties of the discussed ortho-hydroxy Schiff bases than the steric or the environmental effects.     

Calibration of the dianionic phosphate group: Validation on the recognition site of the homodimeric enzyme phosphoglucose isomerase

We calibrate and validate the parameters necessary to represent the dianionic phosphate group (DPG) in molecular mechanics. DPG is an essential fragment of signaling biological molecules and protein-binding ligands. It is a constitutive fragment of biosensors, which bind to the dimer interface of phosphoglucose isomerase (PGI), an intracellular enzyme involved in sugar metabolism, as well as an extracellular protein known as autocrine motility factor (AMF) closely related to metastasis formation. Our long-term objective is to design DPG-based biosensors with enhanced affinities for AMF/PGI cancer biomarker in blood. Molecular dynamics with polarizable potentials could be used toward this aim. This requires to first evaluate the accuracy of such potentials upon representing the interactions of DPG with its PGI ligands and tightly bound water molecules. Such evaluations are done by comparisons with high-level ab initio quantum chemistry (QC) calculations. We focus on the Sum of Interactions Between Fragments Ab initio computed (SIBFA) polarizable molecular mechanics procedure. We present first the results of the DPG calibration. This is followed by comparisons between ΔE(SIBFA) and ΔE(QC) regarding bi-molecular complexes of DPG with the main-chain and side-chain PGI residues, which bind to it in the recognition site. We then consider DPG complexes with an increasing number of PGI residues. The largest QC complexes encompass the entirety of the recognition site, with six structural water molecules totaling up to 211 atoms. A persistent and satisfactory agreement could be shown between ΔE(SIBFA) and ΔE(QC). These validations constitute an essential first step toward large-scale molecular dynamics simulations of DPG-based biosensors bound at the PGI dimer interface. © 2020 Wiley Periodicals, Inc.     

Developing adaptive QM/MM computer simulations for electrochemistry

We report the development of adaptive QM/MM computer simulations for electrochemistry, providing public access to all sources via the free and open source software development model. We present a modular workflow‐based MD simulation code as a platform for algorithms for partitioning space into different regions, which can be treated at different levels of theory on a per‐timestep basis. Currently implemented algorithms focus on targeting molecules and their solvation layers relevant to electrochemistry. Instead of using built‐in forcefields and quantum mechanical methods, the code features a universal interface, which allows for extension to a range of external forcefield programs and programs for quantum mechanical calculations, thus enabling the user to readily implement interfaces to those programs. The purpose of this article is to describe our codes and illustrate its usage. © 2016 Wiley Periodicals, Inc.     

Ab initio simulations of liquid electrolytes for energy conversion and storage

Understanding physicochemical properties of liquid electrolytes is essential for predicting and optimizing device performance for a wide variety of emerging energy technologies, including photoelectrochemical water splitting, supercapacitors, and batteries. In this work, we review recent progress and open challenges in predicting structural, dynamical, and electronic properties of the liquids using first-principles approaches. We briefly summarize the basic concepts of first-principles molecular dynamics (FPMD), and we discuss how FPMD methods have enriched our understanding of a number of liquids, including aqueous solutions, organic electrolytes and ionic liquids. We also discuss technical challenges in extending FPMD simulations to the study of liquid electrolytes in more complex environments, including the interface between electrolytes and electrodes, which is a key component in many energy storage and conversion systems.     

Anisotropic interfacial free energies of the hard-sphere crystal-melt interfaces

We present a reliable method to define the interfacial particles for determining the crystal-melt interface position, which is the key step for the crystal-melt interfacial free energy calculations using capillary wave approach. Using this method, we have calculated the free energies gamma of the fcc crystal-melt interfaces for the hard-sphere system as a function of crystal orientations by examining the height fluctuations of the interface using Monte Carlo simulations. We find that the average interfacial free energy gamma(0) = 0.62 +/- 0.02k(B)T/sigma(2) and the anisotropy of the interfacial free energies are weak, gamma(100) = 0.64 +/- 0.02, gamma(110) = 0.62 +/- 0.02, gamma(111) = 0.61 +/- 0.02k(B)T/sigma(2). The results are in good agreement with previous simulation results based on the calculations of the reversible work required to create the interfaces (Davidchack and Laird, Phys. Rev. Lett. 2000, 85, 4571). In addition, our results indicate gamma(100) > gamma(110) > gamma(111) for the hard-sphere system, similar to the results of the Lennard-Jones system.     

Molecular simulation of hydrophobin adsorption at an oil-water interface

Hydrophobins are small, amphiphilic proteins expressed by strains of filamentous fungi. They fulfill a number of biological functions, often related to adsorption at hydrophobic interfaces, and have been investigated for a number of applications in materials science and biotechnology. In order to understand the biological function and applications of these proteins, a microscopic picture of the adsorption of these proteins at interfaces is needed. Using molecular dynamics simulations with a chemically detailed coarse-grained potential, the behavior of typical hydrophobins at the water-octane interface is studied. Calculation of the interfacial adsorption strengths indicates that the adsorption is essentially irreversible, with adsorption strengths of the order of 100 k(B)T (comparable to values determined for synthetic nanoparticles but significantly larger than small molecule surfactants and biomolecules). The protein structure at the interface is unchanged at the interface, which is consistent with the biological function of these proteins. Comparison of native proteins with pseudoproteins that consist of uniform particles shows that the surface structure of these proteins has a large effect on the interfacial adsorption strengths, as does the flexibility of the protein.     

Modified chemistry of siloxanes under tensile stress: interaction with environment

We present first principles molecular dynamics simulations of stretched siloxane oligomers in an environment representative of that present in single molecule atomic force microscopy experiments. We determine that the solvent used (hexamethyldisiloxane) does not influence the stretching of the siloxane in the high force regime or the rupture process, but trace amounts of water can induce rupture before the maximum siloxane extension has been attained. This would result in a significantly lower rupture force. The simulations show that the rupture of a covalent bond through a reaction with a molecule from the environment, which would not normally occur between the species when the polymer is not stressed, is possible, opening a route to mechanically induced chemical reactions. The attack of the normally hydrophobic siloxane by water when it is stretched has wider implications for the material failure under tensile stress, where trace amounts of water could induce tearing of the material.     

Behavior regulation of adsorbed proteins via hydroxyapatite surface texture control

The influence of nanometer-scale interfaces on proteins has received much attention in recent years. The dynamic behaviors of bone morphogenetic protein-7 (BMP-7) on a series of hydroxyapatite (HAP) surface textures were investigated to explore the influence of different surface textures using molecular dynamics (MD), steered molecular dynamics simulations (SMD), and quantum mechanics calculations. It is observed that the interaction energy curve from SMD simulations can exhibit the dynamic behavior of BMP-7 in detail. Both the type and the number difference of the adsorptive residues and the intensity discrepancy of interaction, which is induced by the specific texture of the HAP surface, could be uncovered from the energy curve qualitatively and semiquantitatively in this study. The largest conformational change occurs in the system 010+a. The quantum mechanics calculations suggest that there is a phenomenon of electron transfer from HAP to the groups of BMP-7 during the adsorption process. These findings suggest that surface-engineering techniques could be employed to directly control the texture of HAP surfaces in order to regulate the behavior of a protein adsorbed onto the nanometer-scale interface.     

Numerical approaches to determine the interface tension of curved interfaces from free energy calculations

A recently proposed method to obtain the surface free energy σ(R) of spherical droplets and bubbles of fluids, using a thermodynamic analysis of two-phase coexistence in finite boxes at fixed total density, is reconsidered and extended. Building on a comprehensive review of the basic thermodynamic theory, it is shown that from this analysis one can extract both the equimolar radius R(e) as well as the radius R(s) of the surface of tension. Hence the free energy barrier that needs to be overcome in nucleation events where critical droplets and bubbles are formed can be reliably estimated for the range of radii that is of physical interest. It is found that the conventional theory of nucleation, where the interface tension of planar liquid-vapor interfaces is used to predict nucleation barriers, leads to a significant overestimation, and this failure is particularly large for bubbles. Furthermore, different routes to estimate the effective radius-dependent Tolman length δ(R(s)) from simulations in the canonical ensemble are discussed. Thus we obtain an instructive exemplification of the basic quantities and relations of the thermodynamic theory of metastable droplets/bubbles using simulations. However, the simulation results for δ(R(s)) employing a truncated Lennard-Jones system suffer to some extent from unexplained finite size effects, while no such finite size effects are found in corresponding density functional calculations. The numerical results are compatible with the expectation that δ(R(s) → ∞) is slightly negative and of the order of one tenth of a Lennard-Jones diameter, but much larger systems need to be simulated to allow more precise estimates of δ(R(s) → ∞).     

Opposing Electronic and Nuclear Quantum Effects on Hydrogen Bonds in H2O and D2O

The effect of extending the O−H bond length(s) in water on the hydrogen-bonding strength has been investigated using static ab initio molecular orbital calculations. The “polar flattening” effect that causes a slight σ-hole to form on hydrogen atoms is strengthened when the bond is stretched, so that the σ-hole becomes more positive and hydrogen bonding stronger. In opposition to this electronic effect, path-integral ab initio molecular-dynamics simulations show that the nuclear quantum effect weakens the hydrogen bond in the water dimer. Thus, static electronic effects strengthen the hydrogen bond in H₂O relative to D₂O, whereas nuclear quantum effects weaken it. These quantum fluctuations are stronger for the water dimer than in bulk water.     

Interfaces in polymer blends

We investigate the structure and thermodynamics of interfaces in dense polymer blends using Monte Carlo (MC) simulations and self‐consistent field (SCF) calculations. For structurally symmetric blends we find quantitative agreement between the MC simulations and the SCF calculations for excess quantities of the interface (e.g., interfacial tension or enrichment of copolymers at the interface). However, a quantitative comparison between profiles across the interface in the MC simulations and the SCF calculations has to take due account of capillary waves. While the profiles in the SCF calculations correspond to intrinsic profiles of a perfectly flat interface the local interfacial position fluctuates in the MC simulations. We test this concept by extensive Monte Carlo simulations and study the cross‐over between “intrinsic” fluctuations which build up the local profile and capillary waves on long (lateral) length scales. Properties of structurally asymmetric blends are exemplified by investigating polymers of different stiffness. At high incompatibilities the interfacial width is not much larger than the persistence length of the stiffer component. In this limit we find deviations from the predictions of the Gaussian chain model: while the Gaussian chain model yields an increase of the interfacial width upon increasing the persistence length, no such increase is found in the MC simulations. Using a partial enumeration technique, however, we can account for the details of the chain architecture on all length scales in the SCF calculations and achieve good agreement with the MC simulations. In blends containing diblock copolymers we investigate the enrichment of copolymers at the interface and the concomitant reduction of the interfacial tension. At weak segregation the addition of copolymers leads to compatibilization. At high incompatibilities, the homopolymer‐rich phase can accommodate only a small fraction of copolymer before the copolymer forms a lamellar phase. The analysis of interfacial fluctuations yields an estimate for the bending rigidity of the interface. The latter quantity is important for the formation of a polymeric microemulsion at intermediate segregation and the consequences for the phase diagram are discussed.     

Simulations of lipid vesicle rupture induced by an adjacent supported lipid bilayer patch

Using a simple phenomenological model of a lipid bilayer and a surface, simulations were performed to study the bilayer-induced vesicle rupture probability as a vesicle adsorbs adjacently to a bilayer patch already adsorbed on the surface. The vesicle rupture probability was studied as a function of temperature, vesicle size, and surface-bilayer interaction strength. From the simulation data, estimates of the apparent activation energy for bilayer-induced vesicle rupture were calculated, both for different vesicle sizes and for different surface-bilayer interaction strengths.     

Efficient solvent boundary potential for hybrid potential simulations

A common challenge in computational biophysics is to obtain statistical properties similar to those of an infinite bulk system from simulations of a system of finite size. In this work we describe a computationally efficient algorithm for performing hybrid quantum chemical/molecular mechanical (QC/MM) calculations with a solvent boundary potential. The system is partitioned into a QC region within which catalytic reactions occur, a spherical region with explicit solvent that envelops the quantum region and is treated with a MM model, and the surrounding bulk solvent that is treated implicitly by the boundary potential. The latter is constructed to reproduce the solvation free energy of a finite number of atoms embedded inside a low-dielectric sphere with variable radius, and takes into account electrostatic and van der Waals interactions between the implicit solvent and the QC and MM atoms in the central region. The method was implemented in the simulation program pDynamo and tested by examining elementary steps in the reaction mechanisms of two enzymes, citrate synthase and lactate dehydrogenase. Good agreement is found for the energies and geometries of the species along the reaction profiles calculated with the method and those obtained by previous experimental and computational studies. Directions in which the utility of the method can be further improved are discussed.     

Some issues on the calculation of interfacial properties by molecular simulation

Some of the pitfalls that may befall molecular simulations of interfaces are discussed. They are all related to the calculation of the pressure tensor profiles, which are needed in order to compute surface tensions. We focus on three controversial points: (1) the calculation of the pressure tensor profiles for polyatomic systems, in particular, when the SHAKE algorithm is employed, (2) the addition of long-range corrections to compensate the truncation of the potential, and (3) the importance of including adequate error intervals with the results. Most of the conclusions are general, but some specifically apply to multiple site molecular-dynamics simulations.     

Rupture work of pendular bridges

Capillary bridging can generate substantial forces between solid surfaces. Impacted technologies and sciences include micro- and nanomachining, disk drive interfaces, scanning probe microscopy, biology, and granular mechanics. Existing calculations of the rupture work of capillary bridges do not consider the thermodynamics relating to the evaporation that can occur in the case of volatile liquids. Here, we show that the occurrence of evaporation decreases the rupture work by a factor of about 2. The decrease arises from heat taken from the surroundings that is converted into work. The treatment is based on a thermodynamic control-volume analysis of the pendular bridge geometry. We extend the mathematical formulation of Orr et al., solving the meniscus problem exactly for non-wetting surfaces. The extension provides analytical results for conditions at the rupture point and at a possible inflection point and for the rupture work. A simple equation (eq 32) is shown to fit the rupture work for the two cases over a meniscus curvature range of 3 orders of magnitude. Coefficients for the equation are given in tabular form for different contact angle pairs.     

Thickness of hydroxyapatite nanocrystal controls mechanical properties of the collagen-hydroxyapatite interface

Collagen-hydroxyapatite interfaces compose an important building block of bone structures. While it is known that the nanoscale structure of this elementary building block can affect the mechanical properties of bone, a systematic understanding of the effect of the geometry on the mechanical properties of this interface between protein and mineral is lacking. Here we study the effect of geometry, different crystal surfaces, and hydration on the mechanical properties of collagen-hydroxyapatite interfaces from an atomistic perspective, and discuss underlying deformation mechanisms. We find that the presence of hydroxyapatite significantly enhances the tensile modulus and strength compared with a tropocollagen molecule alone. The stiffening effect is strongly dependent on the thickness of the mineral crystal until a plateau is reached at 2 nm crystal thickness. We observe no significant differences due to the mineral surface (Ca surface vs OH surface) or due to the presence of water. Our result shows that the hydroxyapatite crystal with its thickness confined to the nanometer size efficiently increases the tensile modulus and strength of the collagen-hydroxyapatite composite, agreeing well with experimental observations that consistently show the existence of extremely thin mineral flakes in various types of bones. We also show that the collagen-hydroxyapatite interface can be modeled with an elastic network model which, based on the results of atomistic simulations, provides a good estimate of the surface energy and other mechanical features.     

Density distribution in the liquid Hg-sapphire interface

We present the results of a computer simulation study of the liquid density distribution normal to the interface between liquid Hg and the reconstructed (0001) face of sapphire. The simulations are based on an extension of the self-consistent quantum Monte Carlo scheme previously used to study the structure of the liquid metal-vapor interface. The calculated density distribution is in very good agreement with that inferred from the recent experimental data of Tamam et al. (J. Phys. Chem. Lett. 2010, 1, 1041-1045). We conclude that, to account for the difference in structure between the liquid Hg-vapor and liquid-Hg-reconstructed (0001) Al(2)O(3) interfaces, it is not necessary to assume there is charge transfer from the Hg to the Al(2)O(3). Rather, the available experimental data are adequately reproduced when the van der Waals interactions of the Al and O atoms with Hg atoms and the exclusion of electron density from Al(2)O(3) via repulsion of the electrons from the closed shells of the ions in the solid are accounted for.     

Application of site binding or surface complexation models to the estimation of the double layer free energy and of the surface pressure of ionizable and ionized surfaces

A modified method for estimating the surface pressure due to adsorbed ions and molecules at oil/water interfaces is presented. This involves general computation methods to determine (a) equilibrium composition resulting from specific reactions in the solution phase and at the interface, and (b) the electrical double layer charges σ_o, σ_β, σ_d and potentials ψ_o, ψ_β, ψ_d based on a site-binding model.Once these properties have been calculated, the surface pressure π of an adsorbed film at oil/water interfaces may be evaluated from an equation of the form:

     

Elucidating the vibrational spectra of hydrogen-bonded aggregates in solution: electronic structure calculations with implicit solvent and first-principles molecular dynamics simulations with explicit solvent for 1-hexanol in n-hexane

Fourier transform infrared spectroscopy is a popular method for the experimental investigation of hydrogen-bonded aggregates, but linking spectral information to microscopic information on aggregate size distribution and aggregate architecture is an arduous task. Static electronic structure calculations with an implicit solvent model, Car-Parrinello molecular dynamics (CPMD) using the Becke-Lee-Yang-Parr (BLYP) exchange and correlation energy functionals and classical molecular dynamics simulations for the all-atom version of the optimized parameters for liquid simulations (OPLS-AA) force field were carried out for an ensemble of 1-hexanol aggregates solvated in n-hexane. The initial configurations for these calculations were size-selected from a distribution of aggregates obtained from a large-scale Monte Carlo simulation. The vibrational spectra computed from the static electronic structure calculations for monomers and dimers and from the CPMD simulations for aggregates up to pentamers demonstrate the extent of the contribution of dangling or nondonating hydroxyl groups found in linear and branched aggregates to the "monomeric" peak. Furthermore, the computed spectra show that there is no simple relationship between peak shift and aggregate size nor architecture, but the effect of hydrogen-bond cooperativity is shown to differentiate polymer-like (cooperative) and dimer-like (noncooperative) hydrogen bonds in the vibrational spectrum. In contrast to the static electronic structure calculations and the CPMD simulations, the classical molecular dynamics simulations greatly underestimate the vibrational peak shift due to hydrogen bonding.     

Molecular dynamics simulations of charged nanoparticle self-assembly at ionic liquid-water and ionic liquid-oil interfaces

Nanoparticle self-assembly at liquid-liquid interfaces can be significantly affected by the individual nanoparticle charges. This is particularly true at ionic liquid (IL) based interfaces, where Coulombic forces play a major role. Employing 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF(6)]) as a model IL, we have studied the self-assembly of hydrophobic nanoparticles with different surface charges at the IL/water and IL/oil (hexane) interfaces using molecular dynamics simulations. In the IL/water system, the nanoparticles were initially dispersed in the water phase but quickly equilibrated at the interface, somewhat in favor of the IL phase. This preference was lessened with increased nanoparticle charge. In the IL/hexane system, all charged nanoparticles interacted with the IL to some extent, whereas the uncharged nanoparticles remained primarily in the hexane phase. Potential of mean force calculations supported the observations from the equilibrium studies and provided new insights into the interactions of the nanoparticles and ionic liquid based interfaces.