Non-bonded Energy Research Articles

Molecular Dynamics Study of Interaction between Acrylamide Copolymers and Alumina Crystal

Four acrylamide polymer flocculants, anionic polyacrylamide P(AA-co-AM), cationic polyacrylamide P(DMB-co-AM), nonionic polyacrylamide P(AM), and hydrophobical polyacrylamide P(OA-co-AM) have been prepared by copolymerizing with acrylic acid, cationic monomer dimethylethyl (acryloxyethyl) ammonium bromide (DMB) and hydrophobical monomer octadecyl acrylate with acrylamide. The interactions between the flocculants with the (012) surface of alumina crystal (Al2O3) have been simulated by molecular dynamics method. All the polymers can bind tightly with Al2O3 crystal, the interaction between the O of polymers and Al of the (012) surface of Al2O3 is significantly strong. The order of binding energy is as follows: P(DMB-co-AM)>P(OA-co-AM)>P(AA-co-AM)>P(AM), implying a better flocculation performance of P(DMB-co-AM) than the others. Analysis indicates that binding energy is mainly determined by Coulomb interaction. Bonds are found between the O atoms of the polymers and the Al atoms of Al2O3. The polymers' structures deform when they combine with Al2O3 crystal, but the deformation energies are low and far less than non-bonding energies. Flocculation experiments in suspension medium of 1%Kaolin show a transmittancy of 90.8% for 6 mg/L P(DMB-co-AM) and 73.0% for P(AM). The sequence of flocculation performance of four polymers is P(DMB-co-AM)>P(OA-co-AM)>P(AA-co-AM)>P(AM), which is in excellent agreement with the simulation results of binding energy.

Structural Hierarchy Controls Deformation Behavior of Collagen

The structure of collagen, the most abundant protein in mammals, consists of a triple helix composed of three helical polypeptide chains. The deformation behavior of collagen is governed by molecular mechanisms that involve the interaction between different helical hierarchies found in collagen. Here, we report results of Steered Molecular Dynamics study of the full-length collagen molecule (~290 nm). The collagen molecule is extended at various pulling rates ranging from 0.00003/ps to 0.012/ps. These simulations reveal a new level of hierarchy exhibited by collagen: helicity of the triple chain. This level of hierarchy is apparent at the 290 nm length and cannot be observed in the 7-9 nm models often described to evaluate collagen mechanics. The deformation mechanisms in collagen are governed by all three levels of hierarchy, helicity of single chain (level-1), helical triple helix (level-2), and hereby described helicity of the triple chain (level-3). The mechanics resulting from the three levels is described by an interlocking gear analogy. In addition, remarkably, the full-length collagen does not show much unwinding of triple helix unlike that exhibited by short collagen models. Further, the full-length collagen does not show significant unwinding of the triple helix, unlike that exhibited by short collagen. Also reported is that the interchain hydrogen bond energy in the full-length collagen is significantly smaller than the overall interchain nonbonded interaction energies, suggesting that the nonbonded interactions have far more important role than hydrogen bonds in the mechanics of collagen. However, hydrogen bonding is essential for the triple helical conformation of the collagen. Hence, although mechanics of collagen is controlled by nonbonded interchain interaction energies, the confirmation of collagen is attributed to the interchain hydrogen bonding.

Volumetric properties of mixtures involving ionic liquids from improved equation of state

The present work aims to propose alternative corresponding states correlations for temperature-dependent parameters appeared in perturbed hard-sphere equation of state (PHS EOS). The microscopic scaling constants σ, the effective hard-sphere diameter, and ɛ, the non-bonded interaction energy between two spheres are employed to construct the correlations. The modified PHS EOS is applied to model the volumetric properties of pure and mixtures containing ionic liquids (ILs). For 3127 experimental density data points examined for the studied pure ILs, the total average absolute deviation (AAD) of the predicted densities from the literature data is found to be 0.52%. Also, 978 data points for binary mixtures is examined, the AAD of the calculated densities of mixtures from those reported in the literature is found to be 0.79%. Several thermodynamic coefficients have also been successfully determined by the use of the present PHS EOS. The effect of the solvent on the excess functions of the studied binary mixtures has also been investigated using the proposed model.

On the accuracy of frozen density embedding calculations with hybrid and orbital-dependent functionals for non-bonded interaction energies

We analyze the accuracy of the frozen density embedding (FDE) method, with hybrid and orbital-dependent exchange-correlation functionals, for the calculation of the total interaction energies of weakly interacting systems. Our investigation is motivated by the fact that these approaches require, in addition to the non-additive kinetic energy approximation, also approximate non-additive exact-exchange energies. Despite this further approximation, we find that the hybrid/orbital-dependent FDE approaches can reproduce the total energies with the same accuracy (about 1 mHa) as the one of conventional semi-local functionals. In many cases, thanks to error cancellation effects, hybrid/orbital-dependent approaches yield even the smallest error. A detailed energy-decomposition investigation is presented. Finally, the Becke-exchange functional is found to reproduce accurately the non-additive exact-exchange energies also for non-equilibrium geometries. These performances are rationalized in terms of a reduced-gradient decomposition of the non-additive exchange energy.

Mechanism of the activation step of the aminoacylation reaction: a significant difference between class I and class II synthetases

In the present work we report, for the first time, a novel difference in the molecular mechanism of the activation step of aminoacylation reaction between the class I and class II aminoacyl tRNA synthetases (aaRSs). The observed difference is in the mode of nucleophilic attack by the oxygen atom of the carboxylic group of the substrate amino acid (AA) to the αP atom of adenosine triphosphate (ATP). The syn oxygen atom of the carboxylic group attacks the α-phosphorous atom (αP) of ATP in all class I aaRSs (except TrpRS) investigated, while the anti oxygen atom attacks in the case of class II aaRSs. The class I aaRSs investigated are GluRS, GlnRS, TyrRS, TrpRS, LeuRS, ValRS, IleRS, CysRS, and MetRS and class II aaRSs investigated are HisRS, LysRS, ProRS, AspRS, AsnRS, AlaRS, GlyRS, PheRS, and ThrRS. The variation of the electron density at bond critical points as a function of the conformation of the attacking oxygen atom measured by the dihedral angle ψ (Cα–C′) conclusively proves this. The result shows that the strength of the interaction of syn oxygen and αP is stronger than the interaction with the anti oxygen for class I aaRSs. This indicates that the syn oxygen is the most probable candidate for the nucleophilic attack in class I aaRSs. The result is further supported by the computation of the variation of the nonbonded interaction energies between αP atom and anti oxygen as well as syn oxygen in class I and II aaRSs, respectively. The difference in mechanism is explained based on the analysis of the electrostatic potential of the AA and ATP which shows that the relative arrangement of the ATP with respect to the AA is opposite in class I and class II aaRSs, which is correlated with the organization of the active site in respective aaRSs. A comparative study of the reaction mechanisms of the activation step in a class I aaRS (Glutaminyl tRNA synthetase) and in a class II aaRS (Histidyl tRNA synthetase) is carried out by the transition state analysis. The atoms in molecule analysis of the interaction between active site residues or ions and substrates are carried out in the reactant state and the transition state. The result shows that the observed novel difference in the mechanism is correlated with the organizations of the active sites of the respective aaRSs. The result has implication in understanding the experimentally observed different modes of tRNA binding in the two classes of aaRSs.

Modeling of P-ρ-T properties of ionic liquids using ISM equation of state: Application to pure component and binary mixtures

Ihm-Song-Mason (ISM) equation of state (EOS) has been previously employed for modeling the volumetric properties of ionic liquids (ILs). The novelty of the present work is in replacing the macroscopic scaling constants with microscopic ones. Three temperature-dependent parameters that appeared in the EOS, which are universal functions of the reduced temperature, were determined using these new microscopic scaling constants. These parameters are the effective hard-sphere diameter (σ) and the non-bonded interaction energy between two spheres (ɛ). The present EOS is evaluated by examination of 3997 experimental density data points for five classes of ILs. The average absolute deviation (AAD) of the calculated densities from literature values was found to be of the order of 0.38%. Our calculations involved a broad range of temperature from 293 K to 472 K and pressures from 0.1MPa up to 200MPa. Another aspect of the present study is the extension of the proposed EOS to predict density of binary mixtures involving IL+ water and IL+ IL. In the case of binary mixtures, 898 data points were taken to assess the capability of the EOS. The overall AAD of the calculated mixture densities from the literature ones was within 0.43%.

New Soft-Core Potential Function for Molecular Dynamics Based Alchemical Free Energy Calculations.

The fields of rational drug design and protein engineering benefit from accurate free energy calculations based on molecular dynamics simulations. A thermodynamic integration scheme is often used to calculate changes in the free energy of a system by integrating the change of the system's Hamiltonian with respect to a coupling parameter. These methods exploit nonphysical pathways over thermodynamic cycles involving particle introduction and annihilation. Such alchemical transitions require the modification of the classical nonbonded potential energy terms by applying soft-core potential functions to avoid singularity points. In this work, we propose a novel formulation for a soft-core potential to be applied in nonequilibrium free energy calculations that alleviates singularities, numerical instabilities, and additional minima in the potential energy for all combinations of nonbonded interactions at all intermediate alchemical states. The method was validated by application to (a) the free energy calculations of a closed thermodynamic cycle, (b) the mutation influence on protein thermostability, (c) calculations of small ligand solvation free energies, and (d) the estimation of binding free energies of trypsin inhibitors. The results show that the novel soft-core function provides a robust and accurate general purpose solution to alchemical free energy calculations.

Pteros: Fast and easy to use open‐source C++ library for molecular analysis

An open-source Pteros library for molecular modeling and analysis of molecular dynamics trajectories for C++ programming language is introduced. Pteros provides a number of routine analysis operations ranging from reading and writing trajectory files and geometry transformations to structural alignment and computation of nonbonded interaction energies. The library features asynchronous trajectory reading and parallel execution of several analysis routines, which greatly simplifies development of computationally intensive trajectory analysis algorithms. Pteros programming interface is very simple and intuitive while the source code is well documented and easily extendible. Pteros is available for free under open-source Artistic License from http://sourceforge.net/projects/pteros/.

Identification of Domains in Protein Structures from the Analysis of Intramolecular Interactions

The subdivision of protein structures into smaller and independent structural domains has a fundamental importance in understanding protein evolution and function and in the development of protein classification methods as well as in the interpretation of experimental data. Due to the rapid growth in the number of solved protein structures, the need for devising new accurate algorithmic methods has become more and more urgent. In this paper, we propose a new computational approach that is based on the concept of domain as a compact and independent folding unit and on the analysis of the residue-residue energy interactions obtainable through classical all-atom force field calculations. In particular, starting from the analysis of the nonbonded interaction energy matrix associated with a protein, our method filters out and selects only those specific subsets of interactions that define possible independent folding nuclei within a complex protein structure. This allows grouping different protein fragments into energy clusters that are found to correspond to structural domains. The strategy has been tested using proper benchmark data sets, and the results have shown that the new approach is fast and reliable in determining the number of domains in a totally ab initio manner and without making use of any training set or knowledge of the systems in exam. Moreover, our method, identifying the most relevant residues for the stabilization of each domain, may complement the results given by other classification techniques and may provide useful information to design and guide new experiments.

Molecular dynamics simulation for interaction of PESA and acrylic copolymers with calcite crystal surfaces

The interactions between four scale inhibitors, namely, polyepoxysuccinic acid (PESA), acrylic acid–maleic acid copolymer[P(AA-co-MA)], acrylic acid–hydroxypropyl acrylate copolymer[P(AA-co-HPA)], acrylic acid–methyl acrylate copolymers[P(AA-co-MAE)] and (104), (11¯0)surfaces of calcite crystal are simulated using a molecular dynamics (MD) method. The results show that the order of corrected binding energy of the four polymers is as follows: PESA>[P(AA-co-MA)]>[P(AA-co-HPA)]>[P(AA-co-MAE)]; however, the interaction of polymers with the (11¯0) surface is significantly stronger (2.5 to 2.8 times) than that with the (104) surface. The binding energy is mainly provided by the ionic bond and the Coulomb interaction, which is verified by analysis of pair correlation functions. The structures of the polymers are deformed during their combining processes with the surfaces. However, the deformation energies are far less than their nonbonding energies respectively. With increasing processing temperature, both the binding energy and the corrected binding energy decrease. The simulation results agree with the static anti-scaling experimental results, which indicate the simulation is correct and reasonable. The simulation results provide theoretical knowledge to assess the performance of scale inhibitors and to synthesize new, highly effective water treatment agents.

Molecular Dynamics Simulation Study Explaining Inhibitor Selectivity in Different Class of Histone Deacetylases

Histone deacetylases (HDACs) are key regulators of gene expression and thereby compelling targets in the treatment of various cancers. Class- and isoform-selective HDAC inhibitors targeting the particular isoform to treat cancers without affecting the normal expression of other isoforms are highly desirable. Molecular dynamics simulations were performed with the set of selective inhibitors and HDAC isoforms of three different classes. The results were compared both within and across the isoforms. The hydrogen bonds between protein and inhibitors are directly correlated with the selective experimental activity. The calculated distances between important amino acids and the metal binding part of inhibitors have disclosed the optimal distance to be maintained by a selective inhibitor. In addition, the calculated non-bonded interaction energies between inhibitor and catalytic residues revealed that the subtle difference in the amino acids at the highly conserved active sites of HDAC isoforms effectively scripts the selectivity story observed experimentally. The results of this study provide valuable information in designing highly selective HDAC inhibitors.

Effect of functionalization on the interfacial binding energy of carbon nanotube/nylon 6 nanocomposites: a molecular dynamics study

The critical challenge for preparing carbon nanotube (CNT)/polymer nanocomposites is how to create a strong interfacial binding energy (IBE) between the polymer matrix and the CNT. Molecular dynamics simulations of nylon 6 melts and its composite with pristine CNT or functionalized CNT embedded have been performed. The properties of the nanocomposites are investigated with the IBE between CNT and nylon 6. The non-bond energies from both vdW and electrostatic interactions, are calculated for nylon 6 and CNT functionalized by different groups. Our calculational results show that the vdW interaction energies of all the functionalized CNT/nylon 6 composites are close to that of the pristine CNT/nylon 6 composite, implicating the electrostatic interactions are responsible for the strong IBE of the functionalized CNT/nylon 6 composites. Therefore, the functionalized CNT can expand the application of polymer in actual production.

Molecular Dynamics Simulation of the SmC Phase

The smectic C phase of a family of calamitic rod-like chiral mesogens was investigated using all-atom molecular dynamics simulation. The studied molecules differ from each other by the orientation of an ester moiety inside the rigid core, the nature of an outboard dipole and the length of the external alkyl chains. Non-bonded potential energy are correlated to experimental mesomorphisms and binary phase diagrams. It is shown that the molecules with the most negative long-range Coulomb potential energy are those that exhibit the greatest ability to experimentally stabilize the smectic C phase.

Characterizing the Mechanical Properties of Graphene and Single Walled Carbon Nanotubes

ABSTRACTIn this study, the mechanical properties of graphene and single walled carbon nanotubes (SWCNTs) were investigated based on molecular dynamics (MD) simulation. During the characterization of the mechanical properties, the atomistic interactions of the carbon atoms were described using the bonded and non-bonded energies. The bonded energy consists of four different interactions: Bond stretching, bond angle bending, dihedral angle torsion, and inversion. On the other hand, the non-bonded interaction between the carbon atoms within the cut-off ranges was regarded as the van der Waals (vdW) force. The effect of vdW force on the mechanical properties of graphene and SWCNTs would be mainly of concern. Simulation results indicated that the Young's modulus of the graphene with vdW force included is 15% higher than that without considering any vdW interaction. The same tendency also was observed in the armchair and zig-zag SWCNTs. Furthermore, it was revealed that the increment of moduli caused by the vdW force could be primarily attributed to the 1-4 vdW interaction. The influence of the vdW interactions on the mechanical properties of graphene and SWCNTs was then elucidated using the parallel spring concept.

Atomistic simulations of the solid-liquid transition of 1-ethyl-3-methyl imidazolium bromide ionic liquid

Achieving melting point around room temperature is important for applications of ionic liquids. In this work, molecular dynamics simulations are carried out to investigate the solid-liquid transition of ionic liquid 1-ethyl-3-methyl imidazolium bromide ([emim]Br) by direct heating, hysteresis, void-nucleation, sandwich, and microcanonical ensemble approaches. Variations of the non-bonded energy, density, diffusion coefficient, and translational order parameter of [emim]Br are analyzed as a function of temperature, and a coexisting solid-liquid system is achieved in the microcanonical ensemble method. The melting points obtained from the first three methods are 547 ± 8 K, 429 ± 8 K, and 370 ± 6 K; while for the sandwich method, the melting points are 403 ± 4 K when merging along the x-axis by anisotropic isothermal-isobaric (NPT) ensemble, 393 ± 4 K when along the y-axis by anisotropic NPT ensemble, and 375 ± 4 K when along the y-axis by isotropic NPT ensemble. For microcanonical ensemble method, when the slabs are merging along different directions (x-axis, y-axis, and z-axis), the melting points are 364 ± 3 K, 365 ± 3 K, and 367 ± 3 K, respectively, the melting points we get by different methods are approximately 55.4%, 21.9%, 5.1%, 14.5%, 11.6%, 6.5%, 3.4%, 3.7%, and 4.3% higher than the experimental value of 352 K. The advantages and disadvantages of each method are discussed. The void-nucleation and microcanonical ensemble methods are most favorable for predicting the solid-liquid transition.

Developing an approach to calculate carbon fiber surface energy using molecular simulation and its application to real carbon fibers

Carbon fiber surface energy is calculated using molecular mechanics simulations on the basis of variation in nonbond energy of carbon fiber due to the presence of various functional groups i.e., OH, CO, and COOH. A step-wise methodology is adopted so that optimized graphite models are used to build separate models of carbon fibers for discrete percentages of OH, CO, and COOH to know the effect of each functional group. Eventually, models of three real carbon fibers are developed to know the combined effect of functional groups on the surface energy of carbon fibers.

An extension strategy of Discovery Studio 2.0 for non-bonded interaction energy automatic calculation at the residue level

Non-bonded interaction forces play crucial roles in molecular recognition and binding in biological systems. However, it is difficult for traditional methods to automatically calculate and batch the non-bonded energy at the residue level. In recent years, many studies have focused on non-bonded interactions and developed tools to calculate and analyze such interactions. In this study, we present a highly automated approach for the calculation of non-bonded energy. Our strategy invoked protocols relevant to non-bonded interactions within Discovery Studio 2.0 (DS2.0, Accelrys Inc.) bottom module using Perl script, and determined the direct command line operation of calculating non-bonded interaction energy batches without accessing the graphical interface of DS. This approach extended the DS2.0 module and was applied to a recent study of complex structure analysis.

Influence of polarity on filling polymer molecules into carbon nanotubes

Using molecular dynamics (MD) simulation, we studied the influence of polarity of polymer chains and modified single-walled nanotubes (SWNTs) on filling polymer chains into SWNTs. The center of mass (COM) distance and the interaction energy between the polymer molecules and SWNTs, as well as non-bond energy (including van der Waals energy and electrostatics energy) differences (ΔE) between initial structure and final structure in the SWNTs–polymers systems were calculated. The simulations indicate that both the polarity of polymer molecules and the polarity of modified groups attached to SWNTs can obstruct filling polymer chains into SWNTs. The general conclusions may be of importance in the production of high-performance SWNTs–polymers nanocomposites and have important theoretical significance on the application of carbon nanotubes as drug carrier and transportation channels.

Molecular modeling of gel nanoparticles with cyclosporine A for oral drug delivery

Structure and behavior of amphiphilogel nanoparticles as a drug carriers for cyclosporine A (CsA) have been studied by the molecular modeling using empirical force field. Five atomistic models of a gel-based emulsions (GEM) with various gel compositions have been investigated in order to find a system most similar to a sixth atomistic model of self-microemulsifying drug delivery system (SMEDDS) taken as an exemplar of CsA delivery system. Structural parameters and energy characteristics (i.e. non-bond interaction energy between CsA and whole remaining components of a gel nanoparticle, CsA/gel nanoparticle intermolecular non-bond interaction energy, CsA–gel molecule pair interaction energy, volume fraction, concentration profiles and number of pervaded water molecules) of these six models in a waterless form and in a water containing form have been studied in dependence on the composition. The Flory–Huggins theory as implemented in the Accelrys Materials Studio 4.2 modeling environment was used to study the pair interactions of cyclosporine A with various types of surfactants. Structural parameters and energy characteristics of all systems have been compared and one composition was selected as a very promising for further experimental study.

Ab-Initio Protein Folding and Small Molecule Dissociation by Potential Energy Based Biased Molecular Dynamics

Molecular dynamics simulations provide increasingly accurate methods for characterizing biomolecular dynamics. However such simulations typically explore dynamics on the ps to ns timescale, while most processes of interest tend to occur on the ms to s timescale. As such there is a need enhanced for sampling methods to overcome this timescale issue. We propose a novel enhanced sampling method in which the dihedral and/or non-bonded potential energy terms are gently biased, such that the system is driven towards lower or higher energy conformations. Preliminary results show particular promise in the area of protein folding and small molecule dissociation. Several small proteins including an alpha helix, hairpin beta sheet, and TRP-CAGE motifs have been folded from extended conformations to within 1 A of their crystal structures with no previous knowledge of said crystal structures. Furthermore, the technique was found to drive dissociation of the avidin-biotin drug complex in under 1 ns. It is anticipated that this method can be extended to all flexible polymers such as DNA, RNA, and proteins. It is also anticipated to increase viability of small molecule binding simulations, allowing for locally enhanced sampling of association/dissociation events.