Influence of the electrostatic interactions on thermophysical properties of polyimides: Molecular‐dynamics simulations

Revealing the way of how modification of the chemical structure of a polymer affects its macroscopic physical properties offers an opportunity to develop novel polymer materials with pre‐defined characteristics. To address this problem two thermoplastic polyimides, ULTEM? and EXTEM?, were simulated with small difference in chemical structures of monomer units, namely, the phenyl ring in ULTEM? was replaced by the diphenylsulphone group in EXTEM?. It is shown that such a small modification results in a drastic difference of the thermal properties: the glass transition temperature of EXTEM? is higher than that of ULTEM?. Our molecular‐dynamics simulations clearly demonstrated that it is the electrostatic interactions that are responsible for the observed difference in thermal properties of ULTEM? and EXTEM?: large partial charges of the sulphone group in the EXTEM? lead to strong dipole–dipole intra‐ and intermolecular interactions and correspondingly to an elevated glass transition temperature. © 2014 Wiley Periodicals, Inc. J. Polym. Sci. Part B: Polym. Phys. 2014 , 52, 640–646     

Parameterization of Ca+2-protein interactions for molecular dynamics simulations

Molecular dynamics simulations of Ca+2 ions near protein were performed with three force fields: GROMOS96, OPLS-AA, and CHARMM22. The simulations reveal major, force-field dependent, inconsistencies in the interaction between the Ca+2 ions with the protein. The variations are attributed to the nonbonded parameterizations of the Ca+2-carboxylates interactions. The simulations results were compared to experimental data, using the Ca+2-HCOO- equilibrium as a model. The OPLS-AA force field grossly overestimates the binding affinity of the Ca+2 ions to the carboxylate whereas the GROMOS96 and CHARMM22 force fields underestimate the stability of the complex. Optimization of the Lennard-Jones parameters for the Ca+2-carboxylate interactions were carried out, yielding new parameters which reproduce experimental data.     

FAMUSAMM: An algorithm for rapid evaluation of electrostatic interactions in molecular dynamics simulations

Within molecular dynamics simulations of protein–solvent systems the exact evaluation of long-range Coulomb interactions is computationally demanding and becomes prohibitive for large systems. Conventional truncation methods circumvent that computational problem, but are hampered by serious artifacts concerning structure and dynamics of the simulated systems. To avoid these artifacts we have developed an efficient and yet sufficiently accurate approximation scheme which combines the structure-adapted multipole method (SAMM) [C. Niedermeier and P. Tavan, J. Chem. Phys., 101 , 734 (1994)] with a multiple-time-step method. The computational effort for MD simulations required within our fast multiple-time-step structure-adapted multipole method (FAMUSAMM) scales linearly with the number of particles. For a system with 36,000 atoms we achieve a computational speed-up by a factor of 60 as compared with the exact evaluation of the Coulomb forces. Extended test simulations show that the applied approximations do not seriously affect structural or dynamical properties of the simulated systems. © 1997 John Wiley & Sons, Inc. J Comput Chem 18 : 1729–1749, 1997     

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.     

Ab initio quantum chemistry and molecular dynamics simulations studies of LiPF6/poly(ethylene oxide) interactions

Ab initio and molecular mechanics studies of LiPF₆ and the interaction of the salt with the poly(ethylene oxide) (PEO) oligomer dimethylether have been performed. Optimized geometries and energies of Li⁺/PF₆^? complexes obtained from quantum chemistry revealed a preference for C_3V symmetry structures for Li⁺–P separations under 2.8 Å, C_2V symmetry for Li⁺–P in the range of 2.8–3.3 Å and C_4V symmetry for Li⁺–P separations larger than 3.3 Å. Electron correlation effects were found to make an insignificant contribution to binding in the Li⁺/PF₆^? complex. By contrast, analogous studies of PF₆^?/PF₆^? and PF₆^?/dimethyl ether complexes revealed important contributions of electron correlation to the complex interaction energy. A molecular mechanics force field for simulations of PEO/LiPF₆ melts was parameterized to reproduce the geometries and energies of Li⁺/PF₆^?, PF₆^?/PF₆^?, PF₆^?/dimethylether complexes. Molecular dynamics simulations of PEO/LiPF₆ melts were performed to validate this quantum chemistry‐based force field. Accurate reproduction of the increase in solution density with addition of salt was found while the electrical conductivity of PEO/LiPF₆ solutions was found to be within an order of magnitude of the experimental values. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 641–654, 2001     

Protonmotive force: development of electrostatic drivers for synthetic molecular motors

Ferrocene has been investigated as a platform for developing protonmotive electrostatic drivers for molecular motors. When two 3-pyridine groups are substituted to the (rapidly rotating) cyclopentadienyl (Cp) rings of ferrocene, one on each Cp, it is shown that the (Cp) eclipsed, pi-stacked rotameric conformation is preferred both in solution and in the solid state. Upon quaternization of both of the pyridines substituents, either by protonation or by alkylation, it is shown that the preferred rotameric conformation is one where the pyridinium groups are rotated away from the fully pi-stacked conformation. Electrostatic calculations indicate that the rotation is caused by the electrostatic repulsion between the charges. Consistently, when the pi-stacking energy is increased pi-stacked population increases, and conversely when the electrostatic repulsion is increased pi-stacked population is decreased. This work serves to provide an approximate estimate of the amount of torque that the electrostatically driven ferrocene platform can generate when incorporated into a molecular motor. The overall conclusion is that the electrostatic interaction energy between dicationic ferrocene dipyridyl systems is similar to the pi-stacking interaction energy and, consequently, at least tricationic systems are required to fully uncouple the pi-stacked pyridine substituents.     

Development of hardware accelerator for molecular dynamics simulations: a computation board that calculates nonbonded interactions in cooperation with fast multipole method

Evaluation of long-range Coulombic interactions still represents a bottleneck in the molecular dynamics (MD) simulations of biological macromolecules. Despite the advent of sophisticated fast algorithms, such as the fast multipole method (FMM), accurate simulations still demand a great amount of computation time due to the accuracy/speed trade-off inherently involved in these algorithms. Unless higher order multipole expansions, which are extremely expensive to evaluate, are employed, a large amount of the execution time is still spent in directly calculating particle-particle interactions within the nearby region of each particle. To reduce this execution time for pair interactions, we developed a computation unit (board), called MD-Engine II, that calculates nonbonded pairwise interactions using a specially designed hardware. Four custom arithmetic-processors and a processor for memory manipulation ("particle processor") are mounted on the computation board. The arithmetic processors are responsible for calculation of the pair interactions. The particle processor plays a central role in realizing efficient cooperation with the FMM. The results of a series of 50-ps MD simulations of a protein-water system (50,764 atoms) indicated that a more stringent setting of accuracy in FMM computation, compared with those previously reported, was required for accurate simulations over long time periods. Such a level of accuracy was efficiently achieved using the cooperative calculations of the FMM and MD-Engine II. On an Alpha 21264 PC, the FMM computation at a moderate but tolerable level of accuracy was accelerated by a factor of 16.0 using three boards. At a high level of accuracy, the cooperative calculation achieved a 22.7-fold acceleration over the corresponding conventional FMM calculation. In the cooperative calculations of the FMM and MD-Engine II, it was possible to achieve more accurate computation at a comparable execution time by incorporating larger nearby regions.     

Accurate conformation‐dependent molecular electrostatic potentials for high‐throughput in silico drug discovery

The atom‐centered partial charges‐approximation is commonly used in current molecular modeling tools as a computationally inexpensive alternative to quantum mechanics for modeling electrostatics. Even today, the use of partial charges remains useful despite significant advances in improving the efficiency of ab initio methods. Here, we report on new parameters for the EEM and SFKEEM electronegativity equalization‐based methods for rapidly determining partial charges that will accurately model the electrostatic potential of flexible molecules. The developed parameters cover most pharmaceutically relevant chemistries, and charges obtained using these parameters reproduce the B3LYP/cc‐pVTZ reference electrostatic potential of a set of FDA‐approved drug molecules at best to an average accuracy of 13 ± 4 kJ mol^?1; thus, equipped with these parameters electronegativity equalization‐based methods rival the current best non‐quantum mechanical methods, such as AM1‐BCC, in accuracy, yet incur a lower computational cost. Software implementations of EEM and SFKEEM, including the developed parameters, are included in the conformer‐generation tool BALLOON , available free of charge at http://web.abo.fi/fak/mnf/bkf/research/johnson/software.php . © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010     

Steered molecular dynamics simulations of protein-ligand interactions

Molecular recognition and specific protein-ligandinteractions are central to many biochemical processes,such as enzyme catalysis, assembly of organelles, en-ergy transduction, signaling, diverse control functions,and replication, expression and storage of the geneticmaterial[1]. Moreover, protein-ligand interactions pro-vide the mechanism of many drug therapies and un-derstanding of such interactions is thus significant forrational drug design[1,2]. For the experimental studiesof protein-ligan…     

Determination of glass transition temperature of polyimides from atomistic molecular dynamics simulations and machine-learning algorithms

Glass transition temperature (T_g) plays an important role in controlling the mechanical and thermal properties of a polymer. Polyimides as an important category of engineering plastics have wide applications because of their superior heat resistance and mechanical strength. The capability of predicting T_g for a polyimide a priori is therefore highly desirable in order to expedite the design and discovery of new polyimide polymers with targeted properties and applications. Here we explore three different approaches to either compute T_g for a polyimide via all-atom molecular dynamics simulations or predict T_g via a mathematical model generated by using machine-learning algorithms to analyze existing data collected from the literature. Our simulations reveal that T_g can be determined from examining the diffusion coefficient of simple gas molecules in a polyimide as a function of temperature and the results are comparable to those derived from data on polymer density versus temperature and actually closer to the available experimental data. Furthermore, the predictive model of T_g derived with machine-learning algorithms can be used to estimate T_g successfully within an uncertainty of about 20 degrees, even for polyimides yet to be synthesized experimentally.     

Optimization of a molecular mechanics force field for type-II polyoxometalates focussing on electrostatic interactions: a case study

In this study, we have focussed on type-II polyanions such as [M(7)O(24)](6-), and we have developed and validated optimized force fields that include electrostatic and van der Waals interactions. These contributions to the total steric energy are described by the nonbonded term, which encompasses all interactions between atoms that are not transmitted through the bonds. A first validation of a stochastic technique based on genetic algorithms was previously made for the optimization of force fields dedicated to type-I polyoxometalates. To describe the new nonbonded term added in the functional, a fixed-charged model was chosen. Therefore, one of the main issues was to analyze that which partial atomic charges could be reliably used to describe these interactions in such inorganic compounds. Based on several computational strategies, molecular mechanics (MM) force field parameters were optimized using different types of atomic charges. Moreover, the influence of the electrostatic and van der Waals buffering constants and 1,4-interactions scaling factors used in the force field were also tested, either being optimized as well or fixed with respect to the values of CHARMM force field. Results show that some atomic charges are not well adapted to CHARMM parameters and lead to unrealistic MM-optimized structures or a MM divergence. As a result, a new scaling factor has been optimized for Quantum Theory of Atoms in Molecules charges and charges derived from the electrostatic potential such as ChelpG. The force fields optimized can be mixed with the CHARMM force field, without changing it, to study for the first time hepta-anions interacting with organic molecules.     

Structural elucidation of dendritic host-guest complexes by X-ray crystallography and molecular dynamics simulations

The multiple monovalent binding of adamantyl-urea poly(propyleneimine) dendrimers with carboxylic acid-urea guests was investigated using molecular dynamics simulations and X-ray crystallography to better understand the structure and behavior of the dynamic multivalent complex in solution. The results from the two methods are consistent and suggest a preferred molecular picture of this complicated aggregate of multiple components. The guest molecules can bind to the dendrimer in a variety of ways although most involve hydrogen-bonding interactions between urea groups of the dendrimer with urea and/or carboxylic acid groups of the guest. In addition, acid-base interactions between the carboxylic acid of the guest and the tertiary amine in the interior of the dendritic host are present. Our proposed structure gives important information about the predominant dynamic interactions between the host and guest and illustrates how they fit together and interact with each other.     

Molecular dynamics in nanostructured polyimide–silica hybrid materials and their thermal stability

Molecular motion and thermal stability in two series of nanophase‐separated polyimide–silica (PI–SiO₂) hybrid materials with chemically bound components were studied. The hybrids were synthesized from p‐aminophenyltrimethoxysilane‐terminated poly(amic acid)s as PI precursors and tetramethoxysilane as a silica precursor via a sol–gel process. The hybrids differed in their PI chemical structure and chain length (number‐average molecular weight = 5.000, 7.500, or 10.000) and in their SiO₂ content, which ranged from 0 to 50 wt %. Differential scanning calorimetry, laser‐interferometric creep rate spectroscopy, and thermally stimulated depolarization current techniques were used for studying the dynamics from 100 to 650 K and from 10^?3 to 10^?2 Hz. Comparative thermogravimetric measurements were also carried out from 300 to 900 K. Silica nano‐ or submicrodomains that formed affected PI dynamics in two opposite directions. Because of the loosening of the molecular packing of PI chains confined to nanometer‐scale spaces between silica constraints, an enhancement of small‐scale motion, mostly at temperatures below the β‐relaxation region, occurred. However, a partial or total suppression of segmental motion could be observed above the β‐relaxation temperature, drastically so for the shortest PI chains at elevated silica contents and within or close to the glass‐transition range, because of the covalent anchoring of chain ends to silica domains. Large changes in thermal stability, including a 2.5‐fold increase in the apparent activation energy of degradation, were observed in the hybrids studied. A greater than 100 °C rise in long‐term thermal stability could be predicted for some hybrids with respect to pure PI. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 1056–1069, 2002     

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.     

Effects of water on epoxy cure kinetics and glass transition temperature utilizing molecular dynamics simulations

Effects of water on epoxy cure kinetics are investigated. Experimental tests show that absorbed water in an uncured bisphenol‐F/diethyl‐toluene‐diamine epoxy system causes an increase in cure rate at low degrees of cure and a decrease in cure rate at high degrees of cure. Molecular simulations of the same epoxy system indicate that the initial increase in cure rate is due to an increase in molecular self‐diffusion of the epoxy molecules in the presence of water. Effects of water on the glass transition temperature (T_g) of the crosslinked thermoset are also studied. Both experiments and simulations show that water decreases T_g. Both types of results indicate that T_g effects are small below 1% water by weight, but that T_g depression occurs much quickly with increasing water content above 1%. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017 , 55, 1150–1159     

A computationally inexpensive modification of the point dipole electrostatic polarization model for molecular simulations

We present an approximation, which allows reduction of computational resources needed to explicitly incorporate electrostatic polarization into molecular simulations utilizing empirical force fields. The proposed method is employed to compute three-body energies of molecular complexes with dipolar electrostatic probes, gas-phase dimerization energies, and pure liquid properties for five systems that are important in biophysical and organic simulations-water, methanol, methylamine, methanethiol, and acetamide. In all the cases, the three-body energies agreed with high level ab initio data within 0.07 kcal/mol, dimerization energies-within 0.43 kcal/mol (except for the special case of the CH(3)SH), and computed heats of vaporization and densities differed from the experimental results by less than 2%. Moreover, because the presented method allows a significant reduction in computational cost, we were able to carry out the liquid-state calculations with Monte Carlo technique. Comparison with the full-scale point dipole method showed that the computational time was reduced by 3.5 to more than 20 times, depending on the system in hand and on the desired level of the full-scale model accuracy, while the difference in energetic results between the full-scale and the presented approximate model was not great in the most cases. Comparison with the nonpolarizable OPLS-AA force field for all the substances involved and with the polarizable POL3 and q90 models for water and methanol, respectively, demonstrates that the presented technique allows reduction of computational cost with no sacrifice of accuracy. We hope that the proposed method will be of benefit to research employing molecular modeling technique in the biophysical and physical organic chemistry areas.     

Comparison of methods for point‐charge representation of electrostatic fields

The calculation of the electrostatic potential resulting from an infinite or extended array of charges in the interior of a region of interest is a frequent task in computational chemistry. In case of a periodic potential this can, for example, be done by Ewald summation or by multipole methods. An important alternative are those methods where arrays of auxiliary point charges are optimized with respect to charge and/or position to reproduce the original electrostatic potential. In the literature different variations are reported. We compare the performance of some of these with respect to their ability to reproduce the original potential and the computational effort required. Between (1) surface charges determined by the conductor‐boundary condition, (2) optimized surface charges, and (3) surface charges floating on the surface we find that (2) offers good quality with small computational costs involved. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004     

Quasi-Hamiltonian equations of motion for internal coordinate molecular dynamics of polymers

Conventional molecular dynamics simulations of macromolecules require long computational times because the most interesting motions are very slow compared to the fast oscillations of bond lengths and bond angles that limit the integration time step. Simulation of dynamics in the space of internal coordinates, that is, with bond lengths, bond angles, and torsions as independent variables, gives a theoretical possibility of eliminating all uninteresting fast degrees of freedom from the system. This article presents a new method for internal coordinate molecular dynamics simulations of macromolecules. Equations of motion are derived that are applicable to branched chain molecules with any number of internal degrees of freedom. Equations use the canonical variables and they are much simpler than existing analogs. In the numerical tests the internal coordinate dynamics are compared with the traditional Cartesian coordinate molecular dynamics in simulations of a 56 residue globular protein. For the first time it was possible to compare the two alternative methods on identical molecular models in conventional quality tests. It is shown that the traditional and internal coordinate dynamics require the same time step size for the same accuracy and that in the standard geometry approximation of amino acids, that is, with fixed bond lengths, bond angles, and rigid aromatic groups, the characteristic step size is 4 fs, which is 2 times higher than with fixed bond lengths only. The step size can be increased up to 11 fs when rotation of hydrogen atoms is suppressed. © 1997 by John Wiley & Sons, Inc. J Comput Chem 18 : 1354–1364, 1997     

Nuclear quantum effects at aqueous metal interfaces captured by molecular dynamics simulations

In this review, we summarize the recent development in modeling nuclear quantum effects at aqueous metal interfaces. First, we review the nuclear quantum effects on the water-metal interface at ultrahigh vacuum. Then, we illustrate the nuclear quantum effects at the potential of zero charge conditions. At last, we give some outlook for the perspective work in modeling the nuclear quantum effects at electrochemical interfaces and some practical simulation strategies.