Full-atom Molecular Dynamics Simulations Research Articles

Entropy-driven segregation in epoxy-amine systems at a copper interface.

The composition of an epoxy resin at the interface with the adherend is usually different from that in the bulk due to the enrichment of a specific constituent, a characteristic called interfacial segregation. For better adhesion, it should be precisely understood how epoxy and amine molecules exist on the adherend surface and react with each other to form a three-dimensional network. In this study, the entropic factor of the segregation in a mixture of epoxy and amine at the copper interface before and after the curing reaction is discussed on the basis of a full-atomistic molecular dynamics (MD) simulation. Smaller molecules were preferentially segregated at the interface regardless of the epoxy and amine, and this segregation remained after the curing process. No segregation occurred at the interface for a combination composed of epoxy and amine molecules with a similar size. These findings make it clear that the size disparity between constituents affects the interfacial segregation via the packing and/or translational entropy. The curing reaction was slower near the interface than in the bulk, and a large amount of unreacted molecules remained there. Finally, the effect of molecular shape was also examined. Linear molecules were more likely to segregate than round-shaped ones even though they were similar in volume. We believe that these findings, which are difficult to obtain experimentally, contribute to the understanding of the interfacial adhesion phenomena on a molecular scale.

Direct observation of morphological transition for an adsorbed single polymer chain

A better understanding of the structure of polymers at solid interfaces is crucial for designing various polymer nano-composite materials from structural materials to nanomaterials for use in industry. To this end, the first step is to obtain information on how synthetic polymer chains adsorb onto a solid surface. We closely followed the trajectory of a single polymer chain on the surface as a function of temperature using atomic force microscopy. Combining the results with a full-atomistic molecular dynamics simulation revealed that the chain became more rigid on the way to reaching a pseudo-equilibrium state, accompanied by a change in its local conformation from mainly loops to trains. This information will be useful for regulating the physical properties of polymers at the interface.

A molecular dynamics study of the binding effectiveness between undoped conjugated polymer binders and tetra-sulfides in lithium–sulfur batteries

Full atomistic molecular dynamics simulations are performed on tetra-sulfides and undoped conjugated polymers pernigraniline base polyaniline (PNB), leucoemeraldine base polyaniline (LEB), poly (3,4-ethylenedioxythiophene) (PEDOT) and polypyrrole (PPY) to investigate the binding effectiveness between polysulfides and polymer binders. The weight ratio between sulfur and binder in lithium–sulfur cells is considered in 1:1 v/v mixture of dioxolane/dimethoxyethane. The simulations reveal that the end group 2 of PNB can effectively bind a lithium tetra-sulfide (i.e. Li2S4) cluster or 2 out of 43 Li2S4 molecules with the effect of solvent. However, repeat units of PNB, LEB, PEDOT and PPY seem ineffective in binding solvated Li2S4 through non-bonded interaction, especially when the concentration of tetra-sulfide/binder in a local domain of the cathode is low. Therefore, polymers with this specific functional group (i.e. the end group 2 of PNB) are suggested to be further studied as potential effective binders to inhibit the shuttle effect of solvated lithium polysulfides. Also, since the solvent has considerable impact on the binding effectiveness between tetra-sulfides and binder, it is suggested to take advantage of the explicit solvation models, such as those built in this work, to predict how other influencing factors affect binding between polysulfides and polymers.

Dynamin-2 R465W mutation induces long range perturbation in highly ordered oligomeric structures

High order oligomers are crucial for normal cell physiology, and protein function perturbed by missense mutations underlies several autosomal dominant diseases. Dynamin-2 is one of such protein forming helical oligomers that catalyze membrane fission. Mutations in this protein, where R465W is the most frequent, cause dominant centronuclear myopathy, but the molecular mechanisms underpinning the functional modifications remain to be investigated. To unveil the structural impact of this mutation in dynamin-2, we used full-atom molecular dynamics simulations and coarse-grained models and built dimers and helices of wild-type (WT) monomers, mutant monomers, or both WT and mutant monomers combined. Our results show that the mutation R465W causes changes in the interactions with neighbor amino acids that propagate through the oligomer. These new interactions perturb the contact between monomers and favor an extended conformation of the bundle signaling element (BSE), a dynamin region that transmits the conformational changes from the GTPase domain to the rest of the protein. This extended configuration of the BSE that is only relevant in the helices illustrates how a small change in the microenvironment surrounding a single residue can propagate through the oligomer structures of dynamin explaining how dominance emerges in large protein complexes.

Local Orientation of Polystyrene at the Interface with Poly(methyl methacrylate) in Block Copolymer.

The local conformation of polystyrene (PS) at the phase-separated lamellar interface with poly(methyl methacrylate) (PMMA) in their diblock copolymer (BCP) was examined by sum-frequency generation spectroscopy in conjunction with a full-atomistic molecular dynamics simulation. While PS phenyl groups of BCP were oriented in the interfacial region, they were random in the bulk. Such an interfacial orientation of phenyl groups was not clear for the corresponding blend of PS and PMMA. The PS backbone of BCP was in-plane oriented and folded near to the chemical junction point located in the interfacial region and the orientation became random at several nanometers distant. No evidence for the chain folding at the interface was found for the blend system.

Combined Modeling of the Optical Anisotropy of Porous Thin Films

In this article, a combined approach for studying the optical anisotropy of porous thin films obtained by the glancing angle deposition is presented. This approach combines modeling on the atomistic and continuum levels. First, thin films clusters are obtained using the full-atomistic molecular dynamics simulation of the deposition process. Then, these clusters are represented as a medium with anisotropic pores, the shapes parameters of which are determined using the Monte Carlo based method. The difference in the main components of the refractive index is calculated in the framework of the anisotropic Bruggeman effective medium theory. The presented approach is tested and validated by comparing the analytical and simulation results for the model problems, and then is applied to silicon dioxide thin films. It is found that the maximum difference between the main components of the refractive index is 0.035 in a film deposited at an angle of 80°. The simulation results agree with the experimental data reported in the literature.

Metallicity-Dependent Ultrafast Water Transport in Carbon Nanotubes.

Carbon nanotubes (CNTs) with hydrophobic and atomically smooth inner channels are promising for building ultrahigh-flux nanofluidic platforms for energy harvesting, health monitoring, and water purification. Conventional wisdom is that nanoconfinement effects determine water transport in CNTs. Here, using full-atomistic molecular dynamics simulations, it is shown that water transport behavior in CNTs strongly correlates with the electronic properties of single-walled CNTs (metallic (met) vs semiconducting (s/c)), which is as dominant as the effect of nanoconfinement. Three pairs of CNTs (i.e., (8,8)met , 10.85 Å vs (9,7)s/c , 10.88 Å; (9,8)s/c , 11.53 Å vs (10,7)met , 11.59 Å; and (9,9)met , 12.20 Å vs (10,8)s/c , 12.23 Å) are used to investigate the roles of diameter and metallicity. Specifically, the (9,8)s/c can restrict the hydrogen-bonding-mediated structuring of water and give the highest reduction in carbon-water interaction energy, providing an extraordinarily high water flux, around 250 times that of the commercial reverse osmosis membranes and approximately fourfold higher than the flux of the state-of-the-art boron nitrate nanotubes. Further, the high performance of (9,8)s/c is also reproducible when embedded in lipid bilayers as synthetic high-water flux porins. Given the increasing availability of high-purity CNTs, these findings provide valuable guides for realizing novel CNT-enhanced nanofluidic systems.

2-Thiobarbituric acid addition improves structural integrity and controlled drug delivery of biocompatible pectin hydrogels

Thiolated polymers are commonly preferred for biomedical applications with their good permeation properties providing them higher bioavailability. However, the thiolation process is mostly time-consuming series of chemical reactions. This study describes a simple irreversible thiol group integration to the pectin hydrogels by noncovalent bonding. We used 2-thiobarbituric acid (TBA) for thiolation. We proved with full-atom molecular dynamics simulations and experimental methods that TBA desertion is negligible. Pectin hydrogels become more flexible and their disintegration is delayed from 4 h up to four days with TBA addition. Also, hydrogels can successfully deliver the model drug, theophylline, showing a controlled release profile.

Exploring the State of the F1-ATPase after ATP Binding and before ADP Release: Effects of Conformational Changes on Phosphate Displacement

Single-molecule imaging experiments provide information that is not available from ensemble experiments. We are interested in the interpretation of dynamical studies imaging and manipulation in F₁-ATPase single-molecules. One key question that has arisen in single molecule stalling experiments is the erratic behavior a rotor angle of 55° between the binding and hydrolysis dwell angles of 0 and 80°, respectively. In our previous theoretical work, we used the elastic property of the rotor-stator structure to treat the experiments on controlled rotation. Our modeling suggests that there has to be a change in the bonding network, for example, of hydrogen bonds, as the system transitions between the two dwell points, perhaps at 55°, as indicated by an unusual stalling behavior around that angle. Therefore, in order to get further insights on these events, we have performed full-atomistic molecular dynamics (MD) simulations on the F₁-ATPase to explore the relationship between the conformational changes and the phosphate displacement. The pK_a values for phosphoric acid are 2.2, 7.2, and 12.3; although the effective pK_a for H₂PO₄⁻ within the binding site could be different. Hence, both protonation states (i.e., H₂PO₄⁻ and HPO₄²⁻) were assessed, performing molecular dynamics for 650 ns at 298.15K (Nose-Hoover thermostat) using the CHARMM36 force field. After the analysis of five MD trajectories, we found that the displacement of the phosphate was, to some extent, correlated with the dynamics of the protein. Moreover, one of the MD trajectories led to the complete release of the diprotic phosphate.

Evaluating Self-Assembly Propensity of Tetra-Peptide using MD and Machine Learning

Evaluation of the self-assembly propensity such as aggregation and amyloid formation of a peptide is important to elucidate protein property. It is also useful in protein engineering for avoiding the aggregation of designed proteins. And, self-assembly structures with high stability are used for nanomaterials. As measuring aggregation propensity of many peptides using experimental methods are difficult, molecular dynamics (MD) simulation has been used for predicting self-assembling peptides. It has been reported that di-peptides (202=400 types) and tri-peptides (203=8000 types) aggregation propensity can be evaluated using MD simulation. However, such methods are difficult to be applied to tetra-peptides due to a large sequence space (204=160,000 types). In this study, we combined the MD simulation and machine learning to accelerate the evaluation of aggregation propensity. We conducted full atomistic MD simulation for 319 peptides and used them for training a machine-learning model to search all possible tetra-peptides. The two scores were used as the measures for self-assembly propensity: AP score related to the accessible surface area of peptides and Beta score related to the possibility of β-sheets structure. We validated that machine learning can accurately predict the result of MD simulation with Pearson's correlation coefficients of 0.88 (AP score) and 0.86 (Beta score). Top 100 predictions suggest that the histidine at C-terminus promotes the formation of a β-sheets structure. We experimentally confirmed that a selected peptide with N-terminal proline predicted to have high AP score and Beta score was aggregated and then changed to fibrous crystals. The crystal structure determined using X-ray diffraction data showed β-sheets structure. These results demonstrate that our framework combining machine learning and MD simulation is a promising strategy for evaluating a property of peptides and proteins.

Erratum to: Molecular dynamics simulations for genetic interpretation in protein coding regions: where we are, where to go and when

The increasing ease with which massive genetic information can be obtained from patients or healthy individuals has stimulated the development of interpretive bioinformatics tools as aids in clinical practice. Most such tools analyze evolutionary information and simple physical-chemical properties to predict whether replacement of one amino acid residue with another will be tolerated or cause disease. Those approaches achieve up to 80-85% accuracy as binary classifiers (neutral/pathogenic). As such accuracy is insufficient for medical decision to be based on, and it does not appear to be increasing, more precise methods, such as full-atom molecular dynamics (MD) simulations in explicit solvent, are also discussed. Then, to describe the goal of interpreting human genetic variations at large scale through MD simulations, we restrictively refer to all possible protein variants carrying single-amino-acid substitutions arising from single-nucleotide variations as the human variome. We calculate its size and develop a simple model that allows calculating the simulation time needed to have a 0.99 probability of observing unfolding events of any unstable variant. The knowledge of that time enables performing a binary classification of the variants (stable-potentially neutral/unstable-pathogenic). Our model indicates that the human variome cannot be simulated with present computing capabilities. However, if they continue to increase as per Moore's law, it could be simulated (at 65°C) spending only 3 years in the task if we started in 2031. The simulation of individual protein variomes is achievable in short times starting at present. International coordination seems appropriate to embark upon massive MD simulations of protein variants.

The interfacial structure and dynamics in a polymer nanocomposite containing small attractive nanoparticles: a full atomistic molecular dynamics simulation study.

We study the interfacial structure and dynamics of a polymer nanocomposite (PNC) composed of octaaminophenyl polyhedral oligomeric silsesquioxane (OAPS) and poly(2-vinylpyridine) (P2VP) by performing full atomistic molecular dynamics simulations. There are eight aminophenyl groups grafted on the surface of the OAPS particle and the particle has a size comparable to the Kuhn segment of P2VP. These aminophenyl groups can form hydrogen bonds (HBs) with pyridine rings from surrounding P2VP chains. We found that OAPS can form ∼2 HBs on average with surrounding polymer chains. The effect of the HBs is investigated in detail by either switching on or off these HBs in our simulation. By analyzing the interfacial static packing structure and dynamic properties, we demonstrate that the system has an ∼1 nm interface width, similar to the OAPS particle size. We also found that HBs can prevent the further penetration of polymers into the inner zone (grafting layer) of the OAPS, and therefore keep the P2VP chains in the outer layer (>1 nm), remaining bulk-like, which is well consistent with experimental results. In addition, we found that NP diffusion is coupled to the absorbed polymer chains, which also dramatically slows down the diffusion of polymer segments in return. The core-shell model in which the NP and absorbed polymers diffuse as a single object is validated here at the full atomistic level. These results provide atomistic insights into the unique structure and dynamics in the small attractive NP-polymer interfacial region. We hope these results will be helpful for the understanding of peculiar phenomena in attractive polymer nanocomposites containing small NPs.

Polynucleotide differentiation using hybrid solid-state nanopore functionalizing with α-hemolysin.

We report results from full atomistic molecular dynamics simulations on the properties of biomimetic nanopores. This latter result was obtained through the direct insertion of an α-hemolysin protein inside a hydrophobic solid-state nanopore. Upon translocation of different DNA strands, we demonstrate here that the theoretical system presents the same discrimination properties as the experimental one obtained previously. This opens an interesting way to promote the stability of a specific protein inside a solid nanopore to develop further biomimetic applications for DNA or protein sequencing.

Molecular dynamics simulations for genetic interpretation in protein coding regions: where we are, where to go and when.

The increasing ease with which massive genetic information can be obtained from patients or healthy individuals has stimulated the development of interpretive bioinformatics tools as aids in clinical practice. Most such tools analyze evolutionary information and simple physical-chemical properties to predict whether replacement of one amino acid residue with another will be tolerated or cause disease. Those approaches achieve up to 80-85% accuracy as binary classifiers (neutral/pathogenic). As such accuracy is insufficient for medical decision to be based on, and it does not appear to be increasing, more precise methods, such as full-atom molecular dynamics (MD) simulations in explicit solvent, are also discussed. Then, to describe the goal of interpreting human genetic variations at large scale through MD simulations, we restrictively refer to all possible protein variants carrying single-amino-acid substitutions arising from single-nucleotide variations as the human variome. We calculate its size and develop a simple model that allows calculating the simulation time needed to have a 0.99 probability of observing unfolding events of any unstable variant. The knowledge of that time enables performing a binary classification of the variants (stable-potentially neutral/unstable-pathogenic). Our model indicates that the human variome cannot be simulated with present computing capabilities. However, if they continue to increase as per Moore's law, it could be simulated (at 65°C) spending only 3years in the task if we started in 2031. The simulation of individual protein variomes is achievable in short times starting at present. International coordination seems appropriate to embark upon massive MD simulations of protein variants.

Molecular Dynamics Study of the Swelling of Poly(methyl methacrylate) in Supercritical Carbon Dioxide.

The swelling of a poly (methyl methacrylate) in supercritical carbon dioxide was studied by means of full atomistic classical molecular dynamics simulation. In order to characterize the polymer swelling, we calculated various properties related to the density, structure, and dynamics of polymer chains as a function of the simulation time, temperature, and pressure. In addition, we compared the properties of the macromolecular chains in supercritical CO2 with the properties of the corresponding bulk system at the same temperature and atmospheric pressure. It was shown that diffusion of CO2 molecules into the polymer led to a significant increase in the chain mobility and distances between them. Analysis of diffusion coefficients of CO2 molecules inside and outside the poly(methyl methacrylate) sample has shown that carbon dioxide actively interacts with the functional groups of poly (methyl methacrylate). Joint analysis of the radial distribution functions obtained from classical molecular dynamics and of the averaging interatomic distances from Car-Parrinello molecular dynamics allows us to make a conclusion about the possibility of formation of weak hydrogen bonds between the carbon dioxide oxygen atom and the hydrogen atoms of the polymer methyl groups.

Investigating the influence of the side-chain pendants of perfluorosulfonic acid membranes in a PEMFC by molecular dynamics simulations

In this study, we used full atomistic molecular dynamics (MD) simulations to evaluate the influence of the side-chain pendants of the PFSA polymer in membranes composed of Nafion or Aquivion ionomers. Despite the lower equivalent weight of the Aquivion ionomer, the Nafion and Aquivion ionomers exhibit similar densities at both room (298.15 K) and operating (353.15 K) temperatures, which leads to higher sulfonic-group/sulfonic-group and sulfonic-group/water-molecule correlations in the Aquivion membrane. We also found that the Aquivion membrane exhibits higher diffusion coefficients for water, hydronium ions, and oxygen molecules than the Nafion membrane. These results are in good agreement with the volume-analysis results, which reveal that the solvent volume is higher in the Aquivion membrane than in the Nafion membrane, which leads to favorable water channels and improved small-molecule diffusion. This study provides PFSA membrane-design insight that can improve PEMFC performance.

Effect of γ-substituted poly(ɛ-caprolactone) chain length on its coil-to-globule transition temperature in water: A molecular dynamics simulation study

The influence of chain length on the coil-to-globule transition temperature (Tcg) of poly{γ-2-[2-(2methoxyethoxy)ethoxy]ethoxy-3-caprolactone} (PMEEECL) chains was investigated via full atomistic molecular dynamics (MD) simulation. Chains with different repeating unit numbers (N) of 5, 10, 15, and 20 were simulated over a wide temperature range. It was found that Tcg increased with increasing N of the PMEEECL chain. The simulation results showed that as the chain contour length is of the order of the Kuhn length, the chain bending and chain collapse become more involved. The chains exhibit significant sensitivity to the temperature when the contour length exceeds the Kuhn length. Nonetheless, for the short chains, i.e. pentamer, the oligomer was temperature insensitive in the studied temperature range. Furthermore, aggregation of five PMEEECL chains with N = 20 was clearly observed at the temperatures above Tcg.

Synthesis, structure and gas separation properties of ethanol-soluble, amphiphilic POM-PBHP comb copolymers

We report the synthesis of a series of alcohol-soluble comb copolymers, specifically poly(oxyethylene methacrylate)-co-poly(2-(4-benzoyl-3-hydroxy phenoxy) ethyl acrylate) (POM-PBHP), with various compositions, as well as their use in CO2 capture membranes. The POM-PBHP comb copolymers were synthesized through a low-cost free-radical polymerization method and analyzed based on Fourier transform infrared spectroscopy and nuclear magnetic resonance. The interactions and structures of the comb copolymers were characterized via X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. The comb copolymers showed good solubility in volatile nontoxic ethanol, allowing them to be coated onto microporous polymer supports to form thin-film composite membranes. While both neat POM and PBHP membranes showed very poor separation properties, the POM-PBHP comb copolymers were effective at separating CO2 from N2. This is because the POM chains with ether oxygen groups have a strong affinity for CO2, leading to high CO2 permeance, whereas the rigid PBHP chains with aromatic rings hinder N2 permeance based on reduced chain mobility. All the full-atomistic molecular dynamics simulations based on density functional theory were also used to characterize the molecular structure and binding energy for CO2, which is consistent with the experimental results. The performance of the membranes was greatest when the content of PBHP in the copolymer was 15 wt%. The CO2/N2 selectivity and CO2 permeability reached 46.6 and 111 Barrer, respectively, which represents one of the highest values for alcohol-soluble, additive-free polymeric membranes and is similar to that of commercial PEBAX membrane.

Molecular dynamics simulations of adsorption of long pyrene-PEG chains on athin carbon nanotube

Carbon nanotubes have emerged as highly promising theranostic agents due to their unique structural/physical features, high surface area, and high drug-loading capacity. The high cytotoxicity of carbon nanotubes can be eliminated by noncovalent coating using hydrophilic polymers. We investigated the adsorption of long pyrene functionalized polyethylene glycol (PEG) chains, PEG$_{2000}$ and PEG$_{5000}$, on a single-walled carbon nanotube (SWNT) from a crowded solution. Full-atom molecular dynamics simulations in explicit water were used to mimic the experimental conditions of noncovalent PEGylation with a stoichiometry of one SWNT to ten pyrene-PEG. Although the diffusional behavior of the pyrene molecules still attached to the polymers did not change according to chain length, the adsorption rate for pyrene-PEG$_{2000}$ to the SWNT was higher than that for pyrene-PEG$_{5000}$ chains. Here longer chains sterically hindered the adsorption of pyrene groups on the SWNT surface. Once adsorbed, pyrene molecules stayed on the SWNT surface even though they frequently adopted different orientations that may weaken their $\pi -\pi $ stacking interactions with the nanotube surface.

Cooperative Effects of Cytosine Methylation on DNA Structure and Dynamics.

The behavior of the structural parameters of DNA considering different levels of methylation in CpG islands is studied by means of full-atom molecular dynamics simulations and electronic circular dichroism, both in an artificial model system and in a gene promoter sequence. It is demonstrated that methylation although intrinsically brings quite local perturbations may, if its level is high enough, induce cooperative effects that strongly modify the DNA backbone torsional parameters altering the helicity as compared to the nonmethylated case. Because methylation of the CpG island is correlated with the regulation of gene expression, understanding the structural modifications induced in DNA is crucial to characterize all the fine equilibria into play in epigenetics phenomena.