A theoretical study of aqueous solvation of K comparing ab initio, polarizable, and fixed-charge models

The hydration of K(+) is studied using a hierarchy of theoretical approaches, including ab initio Born-Oppenheimer molecular dynamics and Car-Parrinello molecular dynamics, a polarizable force field model based on classical Drude oscillators, and a nonpolarizable fixed-charge potential based on the TIP3P water model. While models based more directly on quantum mechanics offer the possibility to account for complex electronic effects, polarizable and fixed-charges force fields allow for simulations of large systems and the calculation of thermodynamic observables with relatively modest computational costs. A particular emphasis is placed on investigating the sensitivity of the polarizable model to reproduce key aspects of aqueous K(+), such as the coordination structure, the bulk hydration free energy, and the self diffusion of K(+). It is generally found that, while the simple functional form of the polarizable Drude model imposes some restrictions on the range of properties that can simultaneously be fitted, the resulting hydration structure for aqueous K(+) agrees well with experiment and with more sophisticated computational models. A counterintuitive result, seen in Car-Parrinello molecular dynamics and in simulations with the Drude polarizable force field, is that the average induced molecular dipole of the water molecules within the first hydration shell around K(+) is slightly smaller than the corresponding value in the bulk. In final analysis, the perspective of K(+) hydration emerging from the various computational models is broadly consistent with experimental data, though at a finer level there remain a number of issues that should be resolved to further our ability in modeling ion hydration accurately.     

Opposite photo-induced deformations in azobenzene-containing polymers with different molecular architecture: molecular dynamics study

Photo-induced deformations in azobenzene-containing polymers (azo-polymers) are central to a number of applications, such as optical storage and fabrication of diffractive elements. The microscopic nature of the underlying opto-mechanical coupling is yet not clear. In this study, we address the experimental finding that the scenario of the effects depends on molecular architecture of the used azo-polymer. Typically, opposite deformations in respect to the direction of light polarization are observed for liquid crystalline and amorphous azo-polymers. In this study, we undertake molecular dynamics simulations of two different models that mimic these two types of azo-polymers. We employ hybrid force field modeling and consider only trans-isomers of azobenzene, represented as Gay-Berne sites. The effect of illumination on the orientation of the chromophores is considered on the level of orientational hole burning and emphasis is given to the resulting deformation of the polymer matrix. We reproduce deformations of opposite sign for the two models being considered here and discuss the relevant microscopic mechanisms in both cases.     

Force fields including charge transfer and local polarization effects: Application to proteins containing multi/heavy metal ions

The question whether molecular dynamics (MD) simulations can yield reliable structural and dynamical properties of metalloproteins depend on the accuracy of the force field, i.e., the potential energy function (PEF) and associated parameters modeling the interactions of the metal ion of interest with water and protein ligands. Previously, we had developed a CTPOL PEF for protein simulations of Zn(2+) bound to Cys(-) and/or His(0) that includes charge transfer and local polarization effects as well as metal van der Waals parameters that reproduce the structural and thermodynamical properties of 22 dications. Here, we evaluate if the CTPOL PEF and the new metal parameters (referred to as the CTPOLa force field) can be applied to proteins containing polynuclear metal-binding sites and heavy toxic metal ions, using the CdZn(2)-Cys(9) beta-domain of rat liver metallothionein-2 and the Hg(2+)-bound 18-residue peptide from MerP as test systems. Using the CTPOLa force field, simulations of the beta-domain of rat liver metallothionein-2 totaling 19 ns could preserve the experimentally observed CdZn(2)-Cys(9) complex geometry and overall protein structure, whereas simulations neglecting charge transfer and local polarization effects could not. However, the CTPOLa force field cannot reproduce the experimentally observed linear bicoordination of Hg(2+) in the MerP peptide without adding an angular restraint to the CTPOL PEF to correct the angle distribution about Hg(2+). Thus, the force fields presented herein for the group IIB metal ions can be applied to simulation studies of proteins containing polynuclear metal-binding sites and heavy metal ions in aqueous solution. PEF neglecting charge transfer and local polarization effects in conjunction with vdW parameters adjusted to reproduce the structural and thermodynamical properties of only the metal ion in question could not yield an accurate representation of the metal-binding site and overall protein structure.     

Water-silica force field for simulating nanodevices

Amorphous silica is an inorganic material that is central for many nanotechnology applications, such as nanoelectronics, microfluidics, and nanopore sensors. To use molecular dynamics (MD) simulations to study the behavior of biomolecules interacting with silica, we developed a force field for amorphous silica surfaces based on their macroscopic wetting properties that is compatible with the CHARMM force field and TIP3P water model. The contact angle of a water droplet on a silica surface served as a criterion to tune the intermolecular interactions. The resulting force field was used to study the permeation of water through silica nanopores, illustrating the influence of the surface topography and the intermolecular parameters on permeation kinetics. We find that minute modeling of the amorphous surface is critical for MD studies, since the particular arrangement of surface atoms controls sensitively electrostatic interactions between silica and water.     

A multistate empirical valence bond description of protonatable amino acids

The multistate empirical valence bond (MS-EVB) model, which was developed for molecular dynamics simulations of proton transport in water and biomolecular systems, is extended for the modeling of protonatable amino acid residues in aqueous environments, specifically histidine and glutamic acid. The parameters of the MS-EVB force field are first determined to reproduce the geometries and energetics of the gas phase amino acid-water clusters. These parameters are then optimized to reproduce experimental pK(a) values. The free energy profiles for acid ionization and the corresponding pK(a) values are calculated by MS-EVB molecular dynamics simulations utilizing the umbrella sampling technique, with the center of excess charge coordinate chosen as the dissociation reaction coordinate. A general procedure for fitting the MS-EVB parameters is formulated, which allows for the parametrization of other amino acid residues with protonatable groups and the subsequent use of the MS-EVB approach for molecular dynamics simulations of proton transfer processes in proteins involving protonation/deprotonation of the protonatable amino acid groups.     

Development of the force field parameters for phosphoimidazole and phosphohistidine

Phosphorylation of histidine-containing proteins is a key step in the mechanism of many phosphate transfer enzymes (kinases, phosphatases) and is the first stage in a wide variety of signal transduction cascades in bacteria, yeast, higher plants, and mammals. Studies of structural and dynamical aspects of such enzymes in the phosphorylated intermediate states are important for understanding the intimate molecular mechanisms of their functioning. Such information may be obtained via molecular dynamics and/or docking simulations, but in this case appropriate force field parameters for phosphohistidine should be explicitly defined. In the present article we describe development of the GROMOS96 force field parameters for phosphoimidazole molecule--a realistic model of the phosphohistidine side chain. The parameterization is based on the results of ab initio quantum chemical calculations with subsequent refinement and testing using molecular mechanics and molecular dynamics simulations. The set of force constants and equilibrium geometry is employed to derive force field for the phosphohistidine moiety. Resulting parameters and topology are incorporated into the molecular modeling package GROMACS and used in molecular dynamics simulations of a phosphohistidine-containing protein in explicit solvent.     

A three-point method for evaluations of AMBER force field parameters: an application to copper-based artificial nucleases

We present the theoretical evaluation of new AMBER force field parameters for 12 copper-based nucleases with bis(2-pyridylmethyl) amine, 2,2′-dipyridylamine, imidazole, N,N-bis(2-benzimidazolylmethyl) amine and their derivative ligands based on first-principles electronic structure calculations at the B3LYP level of theory. A three-point approach was developed to accurately and efficiently evaluate the force field parameters for the copper-based nucleases with the ligands. The protocol of RESP atomic charges has been used to calculate the atomic charge distributions of the studied copper-based nucleases. The evaluated force field parameters and RESP atomic charges have been successfully applied in the testing molecular mechanics calculations and molecular dynamics simulations on the nucleases and the nuclease–DNA complexes, respectively. It has been demonstrated that the developed force field parameters and atomic charges can consistently reproduce molecular geometries and conformations in the available X-ray crystal structures and can reasonably predict the interaction properties of the nucleases with DNA. The developed force field parameters in this work provide an extension of the AMBER force field for its application to computational modeling and simulations of the copper-based artificial nucleases associated with DNA.     

Force field parameters for the simulation of modified histone tails

We describe the development of force field parameters for methylated lysines and arginines, and acetylated lysine for the CHARMM all‐atom force field. We also describe a CHARMM united‐atom force field for modified sidechains suitable for use with fragment‐based docking methods. The development of these parameters is based on results of ab initio quantum mechanics calculations of model compounds with subsequent refinement and validation by molecular mechanics and molecular dynamics simulations. The united‐atom parameters are tested by fragment docking to target proteins using the MCSS procedure. The all‐atom force field is validated by molecular dynamics simulations of multiple experimental structures. In both sets of calculations, the computational predictions using the force field were compared to the corresponding experimental structures. We show that the parameters yield an accurate reproduction of experimental structures. Together with the existing CHARMM force field, these parameters will enable the general modeling of post‐translational modifications of histone tails. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010     

Adsorption and conformation of carboxymethyl cellulose at solid-liquid interfaces using spectroscopic, AFM and allied techniques

Carboxymethyl cellulose (CMC) is a polysaccharide which is widely used in many industrial sectors including food, textiles, paper, adhesives, paints, pharmaceutics, cosmetics and mineral processing. It is a natural organic polymer that is non-toxic and biodegradable. These properties make it ideal for industrial applications. However, a general lack of understanding of the interaction mechanism between the polysaccharides and solid surfaces has hindered the application of this polymer. In this work, adsorption of CMC at the solid-liquid interface is investigated using adsorption and electrophoretic mobility measurements, FTIR, fluorescence spectroscopy, AFM and molecular modeling. CMC adsorption on talc was found to be affected significantly by changes in solution conditions such as pH and ionic strength, which indicates the important role of electrostatic force in adsorption. The pH effect on adsorption was further proven by AFM imaging. Electrokinetic studies showed that the adsorption of CMC on talc changed its isoelectric point. Further, molecular modeling suggests a helical structure of CMC in solution while it is found to adsorb flat on the solid surface to allow its OH groups to be in contact with the surface. Fluorescence spectroscopy studies conducted to investigate the role of hydrophobic bonding using pyrene probe showed no evidence of the formation of hydrophobic domains at talc-aqueous interface. Urea, a hydrogen bond breaker, markedly reduced the adsorption of CMC on talc, supports hydrogen bonding as an important factor. In FTIR study, the changes to the infrared bands, associated with the CO stretch coupled to the CC stretch and OH deformation, were significant and this further supports the strong hydrogen bonding of CMC to the solid surface. In addition, Langmuir modeling of the adsorption isotherm suggests hydrogen bonding to be a dominant force for polysaccharide adsorption since the adsorption free energy of this polymer was close to that for hydrogen bond formation. All of the above results suggest that the main driving forces for CMC adsorption on talc are a combination of electrostatic interaction and hydrogen bonding rather than hydrophobic force.     

Development of a molecular mechanics (MM2) force field for α-chlorosilanes

Molecular mechanics (MM2) parameters for silanes which have a Si-C-Cl fragment have been developed based on available experimental data and ab initio molecular orbital (MO) calculations. Molecular properties, mainly rotational barriers and geometries, of α-chlorosilanes have been studied using our new MM2 parameter set. Changes in the Si-C bond lengths and several bond angles of α-chlorosilanes due to the additional attachment of polar atom(s) have been investigated utilizing ab initio calculations. An electronegativity correction to both bond lengths and angles helps MM2 to reproduce results from ab initio calculations. The new force field has been applied to the conformational analysis of l-(chloromethyl)-1,2-dimethylsilacyclopentane, a model used in our studies of rearrangements of α-halosilanes.     

Dielectric Boundary Forces in Numerical Poisson-Boltzmann Methods: Theory and Numerical Strategies

Continuum modeling of electrostatic interactions based upon the numerical solutions of the Poisson-Boltzmann equation has been widely adopted in biomolecular applications. To extend their applications to molecular dynamics and energy minimization, robust and efficient methodologies to compute solvation forces must be developed. In this study, we have first reviewed the theory for the computation of dielectric boundary forces based on the definition of the Maxwell stress tensor. This is followed by a new formulation of the dielectric boundary force suitable for the finite-difference Poisson-Boltzmann methods. We have validated the new formulation with idealized analytical systems and realistic molecular systems.     

Altered phase model for polymer clay nanocomposites

This paper describes a multiscale approach used to model polymer clay nanocomposites (PCNs) based on a new altered phase concept. Constant-force steered molecular dynamics (SMD) is used to evaluate nanomechanical properties of the constituents of intercalated clay units in PCNs, which were used in the finite element model. Atomic force microscopy and nanoindentation techniques provided additional input to the finite element method (FEM) model. FEM is used to construct a representative PCN model that simulates the composite response of intercalated clay units and the surrounding polymer matrix. From our simulations we conclude that, in order to accurately predict mechanical response of PCNs, it is necessary to take into account the molecular-level interactions between constituents of PCN, which are responsible for the enhanced nanomechanical properties of PCNs. This conclusion is supported by our previous finding that there is a change in crystallinity of polymeric phase due to the influence of intercalated clay units. The extent of altered polymeric phase is obtained from observations of a zone of the altered polymeric phase surrounding intercalated clay units in the "phase image" of PCN surface, obtained using an atomic force microscope (AFM). An accurate FEM model of PCN is constructed that incorporates the zone of the altered polymer. This model is used to estimate elastic modulus of the altered polymer. The estimated elastic modulus for the altered polymer is 4 to 5 times greater than that of pure polymer. This study indicates that it is necessary to take into account molecular interactions between constituents in nanocomposites due to the presence of altered phases, and furthermore provides us with a new direction for the modeling and design of nanocomposites.     

Poly(Lactic Acid)-Based Graft Copolymers: Syntheses Strategies and Improvement of Properties for Biomedical and Environmentally Friendly Applications: A Review

As a potential replacement for petroleum-based plastics, biodegradable bio-based polymers such as poly(lactic acid) (PLA) have received much attention in recent years. PLA is a biodegradable polymer with major applications in packaging and medicine. Unfortunately, PLA is less flexible and has less impact resistance than petroleum-based plastics. To improve the mechanical properties of PLA, PLA-based blends are very often used, but the outcome does not meet expectations because of the non-compatibility of the polymer blends. From a chemical point of view, the use of graft copolymers as a compatibilizer with a PLA backbone bearing side chains is an interesting option for improving the compatibility of these blends, which remains challenging. This review article reports on the various graft copolymers based on a PLA backbone and their syntheses following two chemical strategies: the synthesis and polymerization of modified lactide or direct chemical post-polymerization modification of PLA. The main applications of these PLA graft copolymers in the environmental and biomedical fields are presented.     

Applicability of a modified double lattice model for liquid-liquid equilibria of mixed-solvent polymer systems

Expanding upon a previous study, the modified double lattice model for mixed-solvent polymer systems was developed by employing new universal constants. The calculated results of the proposed model showed good agreement with Monte Carlo simulation results and hypothetically predicted Types 0 and 3 phase separations of the Treybal classification. To describe real systems, the chain length of the polymer and energy parameters were adjusted to fit experimental data. The proposed model correlated well with experimental data from real systems incorporating low to high molecular weight polymers (PEO 200, dextran 40 350, PS 300 000) using reasonable model parameters.     

Equivalent dynamic thermoviscoelastic modeling of ionic polymers

Ionic polymers have attracted considerable attention due to their interesting sensing and actuating behavior which make them a proper choice for use in a wide range of applications including biomimetic robots and biomedical devices. The complicated electro‐chemo‐mechanical dynamics of ionic polymer actuators is a drawback for their applications in functional devices. Therefore, establishing a mathematical model which could effectively predict the actuators' dynamic behavior is of great interest. In this paper, a mathematical model, named equivalent dynamic thermoviscoelastic (EDT) model, based on thermal analogy and beam theory is proposed for dynamic analysis of bending‐type ionic polymer actuators. Then, the developed model is extended for analyzing the performance of the actuator in finite element software. The finite element analysis of the actuator enables consideration of material and geometric nonlinearities and facilitates modeling of functional devices based on the ionic polymer actuators. The proposed modeling approach is validated using experimental data. Copyright © 2015 John Wiley & Sons, Ltd.     

Plasticization of poly(lactide) with blends of tributyl citrate and low molecular weight poly(d,l-lactide)-b-poly(ethylene glycol) copolymers

Polylactide (PLA) is a potential candidate for the partial replacement of petrochemical polymers because it is biodegradable and produced from annually renewable resources. Characterized by its high tensile strength, unfortunately the brittleness and rigidity limit its applicability. For a great number of applications such as packaging, fibers, films, etc., it is of high interest to formulate new PLA grades with improved flexibility and better impact properties.In order to develop PLA-based biodegradable packaging, the physico-mechanical properties of commercially available PLA should be modified using biodegradable plasticizers. To this end, PLA was melt-mixed with blends of tributyl citrate and more thermally stable low molecular weight block copolymers based on poly(d,l-lactide) and poly(ethylene glycol) of different molecular weights and topologies. The copolymers have been synthesized using a potassium based catalyst which is expected to be non toxic and were characterized by utilization of TGA, GPC and NMR techniques.The effect of the addition of up to 25 wt% plasticizer on the thermo-mechanical properties of PLA was investigated and the results were correlated with particular attention to the relationship between properties and applications.To confirm the safety of the catalyst used for the preparation of the copolymers, in vitro cytotoxicity tests have been carried out using MTS assay and the results show their biocompatibility in the presence of the fibroblast cells.Compost biodegradation experiments carried out using neat and plasticized PLA have shown that the presence of plasticizers accelerates the degradation of the PLA matrix.     

Multifunctional properties of 3D printed poly(lactic acid)/graphene nanocomposites by fused deposition modeling

In this work, three-dimensional (3D) printing system based on fused deposition modeling (FDM) is used for the fabrication of conductive polymer nanocomposites. This technology consists in the additive multilayer deposition of polymeric nanocomposite based on poly(lactic acid) (PLA) and graphene by means of a in house made low-cost commercial bench-top 3D printer. Further, 3D printed PLA/graphene nanocomposites containing 10 wt% graphene in PLA matrix were characterized for their mechanical, electrical and electromagnetic induction shielding properties of the nanocomposite. Furthermore X-ray computed micro-tomography analyses showed that printed samples have good dimensional accuracy and are significantly closer to the predefined design and the results of scanning electron microscopy (SEM) printed samples showed a uniform dispersion of graphene in PLA matrix The proposed material has uniquely advantageous when implemented in 3D printed structures, because incorporation of multifunctional graphene has been shown to substantially improve the properties of the resulting nanocomposite.