Classical Mechanical Calculations Research Articles

An improved dataset of force fields, electronic and physicochemical descriptors of metabolic substrates

In silico prediction of xenobiotic metabolism is an important strategy to accelerate the drug discovery process, as candidate compounds often fail in clinical phases due to their poor pharmacokinetic profiles. Here we present MetaQM, a dataset of quantum-mechanical (QM) optimized metabolic substrates, including force field parameters, electronic and physicochemical properties. MetaQM comprises 2054 metabolic substrates extracted from the MetaQSAR database. We provide QM-optimized geometries, General Amber Force Field (FF) parameters for all studied molecules, and an extended set of structural and physicochemical descriptors as calculated by DFT and PM7 methods. The generated data can be used in different types of analysis. FF parameters can be applied to perform classical molecular mechanics calculations as exemplified by the validating molecular dynamics simulations reported here. The calculated descriptors can represent input features for developing improved predictive models for metabolism and drug design, as exemplified in this work. Finally, the QM-optimized molecular structures are valuable starting points for both ligand- and structure-based analyses such as pharmacophore mapping and docking simulations.

Crystal Polymorph Search in the NPT Ensemble via a Deposition/Sublimation Alchemical Path.

The formulation of active pharmaceutical ingredients involves discovering stable crystal packing arrangements or polymorphs, each of which has distinct pharmaceutically relevant properties. Traditional experimental screening techniques utilizing various conditions are commonly supplemented with in silico crystal structure prediction (CSP) to inform the crystallization process and mitigate risk. Predictions are often based on advanced classical force fields or quantum mechanical calculations that model the crystal potential energy landscape but do not fully incorporate temperature, pressure, or solution conditions during the search procedure. This study proposes an innovative alchemical path that utilizes an advanced polarizable atomic multipole force field to predict crystal structures based on direct sampling of the NPT ensemble. The use of alchemical (i.e., nonphysical) intermediates, a novel Monte Carlo barostat, and an orthogonal space tempering bias combine to enhance the sampling efficiency of the deposition/sublimation phase transition. The proposed algorithm was applied to 2-((4-(2-(3,4-dichlorophenyl)ethyl)phenyl)amino)benzoic acid (Cambridge Crystallography Database Centre ID: XAFPAY) as a case study to showcase the algorithm. Each experimentally determined polymorph with one molecule in the asymmetric unit was successfully reproduced via approximately 1000 short 1 ns simulations per space group where each simulation was initiated from random rigid body coordinates and unit cell parameters. Utilizing two threads of a recent Intel CPU (a Xeon Gold 6330 CPU at 2.00 GHz), 1 ns of sampling using the polarizable AMOEBA force field can be acquired in 4 h (equating to more than 300 ns/day using all 112 threads/56 cores of a dual CPU node) within the Force Field X software (https://ffx.biochem.uiowa.edu). These results demonstrate a step forward in the rigorous use of the NPT ensemble during the CSP search process and open the door to future algorithms that incorporate solution conditions using continuum solvation methods.

Characterization and Molecular Modelling of Non-Antibiotic Nanohybrids for Wound Healing Purposes.

The healing process of chronic wounds continues to be a current clinical challenge, worsened by the risk of microbial infections and bacterial resistance to the most frequent antibiotics. In this work, non-antibiotic nanohybrids based on chlorhexidine dihydrochloride and clay minerals have been developed in order to design advanced therapeutic systems aimed to enhance wound healing in chronic lesions. To prepare the nanohybrids, two methodologies have been compared: the intercalation solution procedure and the spray-drying technique, the latter as a one-step process able to reduce preparation times. Nanohybrids were then fully studied by solid state characterization techniques. Computational calculations were also performed to assess the interactions between the drug and the clays at the molecular level. In vitro human fibroblast biocompatibility and antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa were assessed to check biocompatibility and potential microbicidal effects of the obtained nanomaterials. The results demonstrated the effective organic/inorganic character of the nanohybrids with homogeneous drug distribution into the clayey structures, which had been confirmed by classical mechanics calculations. Good biocompatibility and microbicidal effects were also observed, especially for the spray-dried nanohybrids. It was suggested that it could be due to a greater contact area with target cells and bacterial suspensions.

Toward Addressing the Challenge to Predict the Heat Capacities of RDX and HMX Energetic Materials

AbstractAvailability of heat capacity as a function of pressure and temperature is an essential prerequisite for development of a computational multiscale strategy capable to address the evolution of microstructure and energy release in advanced high energy density materials. In the case of 1,3,5‐trinitro‐1,3,5‐triazinane (RDX) and 1,3,5,7‐tetranitro‐1,3,5,7‐tetrazocane (HMX) systems as two of the most studied energetic materials, there are substantial gaps in experimental data, with available heat capacities values distributed only in a region close to standard ambient conditions. In this study we demonstrate how these major experimental limitations can be addressed in the case of the RDX and HMX systems based on the combined use of classical and quantum mechanical calculations. We show that by considering ideal gas properties evaluated using quantum mechanical methods, and residual properties obtained from molecular simulations using fully flexible atomistic force field models, excellent agreement can be obtained for the predicted heat capacities to the most recent experimental values. An important advantage of the current computational methodology is that it allows evaluation of both constant‐volume and constant‐pressure heat capacities for a broad interval of temperatures and pressures, which encompasses solid and liquid phases conditions. In the case of the solid α and γ phases of RDX and the β phase of HMX, the predicted results follow closely both the available experimental data at standard ambient conditions and the results obtained using density functional theory calculations at high pressures, a regime where experimental data are not available. A perspective to expand the current methodology is also discussed.

Numerical-continuation-enhanced flexible boundary condition scheme applied to mode-I and mode-III fracture.

Motivated by the inadequacy of conducting atomistic simulations of crack propagation using static boundary conditions that do not reflect the movement of the crack tip, we extend Sinclair's flexible boundary condition algorithm [J. E. Sinclair, Philos. Mag. 31, 647 (1975)PHMAA40031-808610.1080/14786437508226544] and propose a numerical-continuation-enhanced flexible boundary scheme, enabling full solution paths for cracks to be computed with pseudo-arclength continuation, and present a method for incorporating more detailed far-field information into the model for next to no additional computational cost. The algorithms are ideally suited to study details of lattice trapping barriers to brittle fracture and can be incorporated into density functional theory and multiscale quantum and classical quantum mechanics and molecular mechanics calculations. We demonstrate our approach for mode-III fracture with a 2D toy model and employ it to conduct a 3D study of mode-I fracture of silicon using realistic interatomic potentials, highlighting the superiority of the approach over employing a corresponding static boundary condition. In particular, the inclusion of numerical continuation enables converged results to be obtained with realistic model systems containing a few thousand atoms, with very few iterations required to compute each new solution. We also introduce a method to estimate the lattice trapping range of admissible stress intensity factors K_{-}<K<K_{+} very cheaply and demonstrate its utility on both the toy and realistic model systems.

Glory oscillations in photoionization microscopy: Connection with electron dynamics and Stark spectral structures in the continuum

In classical scattering theory, the term “glory scattering” implies the divergence of the classical differential cross section that occurs as soon as the deflection function goes through zero for a nonzero value of the impact parameter. This critical effect also occurs in slow photoelectron imaging where near-threshold atomic photoionization is performed in the presence of an external static electric field. In this case, glory scattering manifests itself by the appearance of an intense peak at the center of the photoelectron momentum distribution. In the present work we examine the magnitude variation of this central peak as a function of electron energy. We experimentally study near-threshold two-photon ionization of ground state magnesium atoms, below as well as above the field-free ionization limit. It is found that, apart from its behavior of classical origin, the glory signal additionally exhibits strong oscillations and beating effects over the full spectral range of the recordings. Of particular interest are its oscillations above the zero-field limit, many aspects of which are expected to be independent of the atomic target. Our results are analyzed with the help of classical, semiclassical, and quantum mechanical calculations devoted to the hydrogenic Stark effect. It is theoretically found that these continuum glory oscillations are related to the resonantlike Stark structures appearing under certain conditions in the total photoionization cross section and implying energy quantization in the continuum. The striking outcome of the present study, however, is that both theory and experiment clearly support the connection between the energy- and static field-dependent periodicity of glory oscillations with the classical dynamics of electron motion. In particular, it is shown that the Fourier transform of the glory signal provides information on the differences between the origin-to-detector times of flight corresponding to specific pairs of classical electron trajectories.

Interaction of cobalt and iron hydroperoxo bleomycin with deoxyribonucleic acid (DNA): Dynamic vs. electronic structure considerations

Classical molecular mechanics and quantum mechanical dynamics calculations of iron and cobalt hydroperoxo adducts of bleomycin with deoxyribonucleic acid (DNA) yield structures in reasonable agreement with the experimentally-known Co structures. The hydroxyl (OH) group of the metal-bound hydroperoxide is predicted to reside very close to a deoxyribose proton in the Co-hydroperoxo-DNA adduct (in agreement with experiment) as well as in the ferric counterpart (for which no structural data is available from experiments). According to density functional theory calculations, this sterical arrangement leads to facile insertion of the peroxide OH into the sugar within the Fe(III) but not in the Co(III)-hydroperoxo-bleomycin-DNA complex. However, experiments reveal that the peroxo oxygen is in fact not inserted into the product – at odds with the quantum mechanical calculations. On the other hand, the computed dynamics of the peroxide-sugar distance involve occasional movement of the peroxide ~1.5 Å further away from the CH bond, providing an opportunity for Fe(III)O-OH bond cleavage without immediately trapping the departing OH onto the deoxyribose. Also, while the peroxide moiety in the DNA-bleomycin complex is on average well shielded from the solvent, the dynamics calculations reveal occasional opening of this shielding on nanosecond timescales; individual snapshots are identified, where water molecules from the solvent are in direct contact with the iron-bound hydroperoxide in the bleomycin-DNA complex. Therefore, the general picture provided by molecular dynamics simulations is one where the oxygen–oxygen bond is initially cleaved to generate a high-valent intermediate, which can oxidize the deoxyribose in an outer-sphere manner

Hydrophobic but Water-Friendly: Favorable Water-Perfluoromethyl Interactions Promote Hydration Shell Defects.

Although perfluorination is known to enhance hydrophobicity and change protein activity, its influence on hydration-shell structure and thermodynamics remains an open question. Here we address that question by combining experimental Raman multivariate curve resolution spectroscopy with theoretical classical simulations and quantum mechanical calculations. Perfluorination of the terminal methyl group of ethanol is found to enhance the disruption of its hydration-shell hydrogen bond network. Our results reveal that this disruption is not due to the associated volume change but rather to the electrostatic stabilization of the water dangling OH···F interaction. Thus, the hydration shell structure of fluorinated methyl groups results from a delicate balance of solute-water interactions that is intrinsically different from that associated with a methyl group.

Classical and Quantum Analysis of Lithium Anodes in Nanobattery Models

We report our studies of lithium-metal anodes as part of a nanobattery with the goal of improving conditions under which the anode material can be successfully used. This work is performed using multiscale classical and quantum mechanical calculations. Specifically, we use the classical and quantum molecular dynamics atomistic simulations with liquid and solid electrolytes of different sizes. Thus, in this effort in progress, we are focusing on the electrical properties such as polarization conductivity as well as on mechanical and chemical properties such as swelling, alloying, amorphization and speciation on the anode material and in its solid-electrolyte interphase (SEI), during the first charging cycles. The nanobattery includes most of the important components of a real battery such as the cathode, the electrolyte solution (solid or liquid), the anode, and the current collectors. External electric fields are applied under classical and quantum regimes to emulate the charging process causing the migration of the Li-ions from the cathode, drifting through the electrolyte to finally get into the anode. We immediately observed during charging of the nanobattery, how some other anodes change gradually producing cracks of the SEI and then dendrites. We obtained the drift velocity of the Li-ions during the amorphization of the anodes as the original volume of the anode increases. Our nanobattery model can be used to study the mechanisms taking place at the electrolyte and electrodes interfaces, and especially for guidance, and discovery of new materials. Our results are helping us to understand the mechanics and chemistry of future batteries, specially to prevent undesirable effects such as the cracking of the anode and dendrite formation.

Generation of ultrashort X-ray bursts without attosecond frequency modulation in Coulomb collisions of nuclei of diatomic heteronuclear molecules ionised by an ultraintense laser pulse

Based on classical and quantum mechanical calculations, we study the possibility of generating ultrashort X-ray bursts, free of attosecond frequency modulation (attochirp), with photon energies of the order of 1 keV and higher in Coulomb collisions of nuclei in an ensemble of diatomic molecules containing nuclei with different masses, driven by ultraintense IR laser pulses. The minimally attainable duration of the generated X-ray pulses is investigated as a function of intensity and wavelength of laser radiation. It is shown that the considered mechanism of nuclear collisions makes it possible to generate transform-limited X-ray pulses with a duration of about 1 as using modern petawatt laser systems.

Classical and Quantum Mechanical Calculations of the Stacking Interaction of NdIII Complexes with Regular and Mismatched DNA Sequences.

The design of organometallic complexes used as selective intercalators to bind and react at DNA mismatch sites has concentrated efforts in the last few years. In this context, lanthanides have received attention to be employed as active optical centers due to their spectroscopic properties. Despite the fact that there are several experimental data about synthesis and DNA binding of these compounds, theoretical analyses describing their interaction with DNA are scarce. To understand the binding to regular and mismatched DNA sequences as well as to determine the effect of the intercalation on the spectroscopic properties of the complexes, a complete theoretical study going from classical to relativistic quantum mechanics calculations has been performed on some lanthanide complexes with phenanthroline derivatives synthesized and characterized herein, viz. [Nd(NO3)3(H2O)(dppz-R)] with R = H, NO2-, CN- and their [Nd(NO3)3(H2O)(dpq)] analogue, which was computationally modeled. The results were in correct agreement with the available experimental data showing that dppz complexes have higher binding affinities to DNA than dpq one and supporting the idea that these complexes are not selective to mismatch sites in the sampled time scale. Finally, the spectroscopic analysis evidence an intercalative binding mode and made possible the elucidation of the emission mechanism of these systems. This approach is proposed as a benchmark study to extend this methodology on similar systems and constitutes the first theoretical insight in the interaction between DNA and lanthanide complexes.

Rose Bengal incorporated to α-cyclodextrin microparticles for photodynamic therapy against the cariogenic microorganism Streptococcus mutans.

Rose Bengal@α-cyclodextrin (RB@α-CD) microparticles (μPs) were prepared and the RB inclusion in α-CD was experimentally demonstrated through infrared, UV-VIS absorption spectroscopy and cyclic voltammetry. The RB inclusion in α-CD was theoretically investigated using classical molecular mechanics calculations, the simulation results showing that RB can be included in both the narrow and wide apertures of the α-cyclodextrin ring with configurations exhibiting average binding energies of about 27 kcal mol-1. The prepared RB@α-CD microparticles were characterized through Scanning Electron Microscopy (SEM) and it was demonstrated that they are highly efficient in the photodynamic therapy against a Streptococcus mutans (the main bacteria of cariogenic dental plaque) suspension, as a concentration of RB@α-CD μPs 10 times smaller than the usual concentration of pure RB is still capable to produce significant antibacterial activity.

Artificial neural networks and intelligent finite elements in non-linear structural mechanics

In recent years, artificial neural networks were included in the prediction of deformations of structural elements, such as pipes or tensile specimens. Following this method, classical mechanical calculations were replaced by a set of matrix multiplications by means of artificial intelligence. This was also continued in finite element approaches, wherein constitutive equations were substituted by an artificial neural network (ANN). However, little is known about predicting complex non-linear structural deformations with artificial intelligence. The aim of the present study is to make ANN accessible to complicated structural deformations. Here, shock-wave loaded plates are chosen, which lead to a boundary value problem taking geometrical and physical non-linearities into account. A wide range of strain-rates and highly dynamic deformations are covered in this type of deformation. One ANN is proposed for the entire structural model and another ANN is developed for replacing viscoplastic constitutive equations, integrated into a finite element code, leading to an intelligent finite element. All calculated results are verified by experiments with a shock tube and short-time measurement techniques.

Electronic and thermoelectric properties of atomically thin C3Si3/C and C3Ge3/C superlattices

The nanostructuring of graphene into superlattices offers the possibility of tuning both the electronic and thermal properties of graphene. Using classical and quantum mechanical calculations, we have investigated the electronic and thermoelectric properties of the atomically thin superlattice of C3Si3/C (C3Ge3/C) formed by the incorporation of Si (Ge) atoms into graphene. The bandgap and phonon thermal conductivity of C3Si3/C (C3Ge3/C) are 0.54 (0.51) eV and 15.48 (12.64) W m−1 K−1, respectively, while the carrier mobility of C3Si3/C (C3Ge3/C) is 1.285 × 105 (1.311 × 105) cm2 V−1 s−1 at 300 K. The thermoelectric figure of merit for C3Si3/C (C3Ge3/C) can be optimized via the tuning of carrier concentration to obtain the prominent ZT value of 1.95 (2.72).

Sensing inhomogeneous mechanical properties of human corneal Descemet's membrane with AFM nano-indentation

The paper describes a highly space-resolved characterization of the surface mechanical properties of the posterior human corneal layer (Descemet's membrane). This has been accomplished with Atomic Force Microscopy (AFM) nano-indentation by using a probe with a sharp tip geometry. Results indicate that the contact with this biological tissue in liquid occurs with no (or very low) adhesion. More importantly, under the same operating conditions, a broad distribution of penetration depth can be measured on different x-y positions of the tissue surface, indicating a high inhomogeneity of surface stiffness, not yet clearly reported in the literature. An important contribution to such inhomogeneity should be ascribed to the discontinuous nature of the collagen/proteoglycans fibers matrix tissue, as can be imaged by AFM when the tissue is semi-dry.Using classical contact mechanics calculations adapted to the specific geometry of the tetrahedral tip it has been found that the elastic modulus E of the material in the very proximity of the surface ranges from 0.23 to 2.6 kPa.

A charge equilibration formalism for treating charge transfer effects in MD simulations: Application to water clusters.

Conventional classical force fields by construction do not explicitly partition intermolecular interactions to include polarization and charge transfer effects, whereas fully quantum mechanical treatments allow a means to effect this dissection (although not uniquely due to the lack of a charge transfer operator). Considering the importance of polarization in a variety of systems, a particular class of classical models, charge equilibration models, have been extensively developed to study those systems; since these types of interaction models are inherently based on movement of charge throughout a system, they are natural platform for including polarization and charge transfer effects within the context of molecular simulations. Here, we present two bond-space charge equilibration models we term as QE2 and mixed QE2 treat charge transfer in classical molecular mechanical calculations those provide practical solutions to two major drawbacks of charge equilibration models: (a) a nonvanishing amount of charge transfer between two heteroatoms at large separations, and (b) superlinear polarizability scaling during bond dissociation due to charge transfer over unphysical, large distances. To control charge transfer during dissociation of a bond in a molecular system, we introduce a distance-dependent scaling function (QE2 model) which, controls and recovers physical behavior of the homonuclear and heteronuclear charge transfer between two atoms at small and large values of internuclear separation; and the mixed QE2 model in which we combine the QE2 model under allow and disallow charge transfer situations that describe both charge transfer and polarizability in a distance-dependent manner. We demonstrate the utility of both models in the case of a water dimer, and compare the results with other existing models, and further, we perform short molecular dynamics simulations for few water clusters with the QE2 model to show the charge transfer and internuclear separation are correlated in dynamics. © 2017 Wiley Periodicals, Inc.

Significantly reduced thermal conductivity and enhanced thermoelectric properties of single- and bi-layer graphene nanomeshes with sub-10 nm neck-width

When graphene is shrunk into ~10nm scale graphene nanoribbons or nanomesh structures, it is expected that not only electrical properties but also thermal conductivity and thermoelectric property are significantly altered due to the quantum confinement effect and extrinsic phonon-edge scattering. Here, we fabricate large-area, sub-10nm single- and bilayer graphene nanomeshes from block copolymer self-assembly and measure the thermal conductivity, thermoelectric and electrical transport properties to experimentally verify the effect of sub-10nm quantum confinement, phonon-edge scattering and cross-plane coupling. Among the large variety of the samples, bilayer graphene nanomesh having 8nm-neck width showed significantly low thermal conductivity down to ~78Wm−1K−1, which is the lowest thermal conductivity for suspended graphene nanostructures, and a high thermopower value of −520μVK−1, while it still shows the comparably high carrier mobility. Classical and quantum mechanical calculations successfully supported our nanomesh approach, which can achieve high thermoelectric properties based on the significantly reduced thermal conductivity and higher thermopower due to the confined geometry.

Identifying the receptor subtype selectivity of retinoid X and retinoic acid receptors via quantum mechanics.

Understanding and identifying the receptor subtype selectivity of a ligand is an important issue in the field of drug discovery. Using a combination of classical molecular mechanics and quantum mechanical calculations, this report assesses the receptor subtype selectivity for the human retinoid X receptor (hRXR) and retinoic acid receptor (hRAR) ligand‐binding domains (LBDs) complexed with retinoid ligands. The calculated energies show good correlation with the experimentally reported binding affinities. The technique proposed here is a promising method as it reveals the origin of the receptor subtype selectivity of selective ligands.

Understanding decomposition and encapsulation energies of structure I and II clathrate hydrates.

When compressed with water or ice under high pressure and low temperature conditions, some gases form solid gas hydrate inclusion compounds which have higher melting points than ice under those pressures. In this work, we study the balance of the guest-water and water-water interaction energies that lead to the formation of the clathrate hydrate phases. In particular, molecular dynamics simulations with accurate water potentials are used to study the energetics of the formation of structure I (sI) and II (sII) clathrate hydrates of methane, ethane, and propane. The dissociation enthalpy of the clathrate hydrate phases, the encapsulation enthalpy of methane, ethane, and propane guests in the corresponding phases, and the average bonding enthalpy of water molecules are calculated and compared with accurate calorimetric measurements and previous classical and quantum mechanical calculations, when available. The encapsulation energies of methane, ethane, and propane guests stabilize the small and large sI and sII hydrate cages, with the larger molecules giving larger encapsulation energies. The average water-water interactions are weakened in the sI and sII phases compared to ice. The relative magnitudes of the van der Waals potential energy in ice and the hydrate phases are similar, but in the ice phase, the electrostatic interactions are stronger. The stabilizing guest-water "hydrophobic" interactions compensate for the weaker water-water interactions and stabilize the hydrate phases. A number of common assumptions regarding the guest-cage water interactions are used in the van der Waals-Platteeuw statistical mechanical theory to predict the clathrate hydrate phase stability under different pressure-temperature conditions. The present calculations show that some of these assumptions may not accurately reflect the physical nature of the interactions between guest molecules and the lattice waters.

Optimization of the Thermoelectric Figure of Merit in Crystalline C60 with Intercalation Chemistry.

Crystalline C60 is an appealing candidate material for thermoelectric (TE) applications due to its extremely low thermal conductivity and potentially high electrical conductivity with metal atom intercalation. We investigate the TE properties of crystalline C60 intercalated with alkali and alkaline earth metals using both classical and quantum mechanical calculations. For the electronic structure, our results show that variation of intercalated metal atoms has a large impact on energy dispersions, which leads to broad tunability of the power factor. For the thermal transport, we show that dopants introduce strong phonon scattering into crystalline C60, leading to considerably lower thermal conductivity. Taking both into account, our calculations suggest that appropriate choice of metal atom intercalation in crystalline C60 could yield figures of merit near 1 at room temperature.