Large-scale Atomistic Simulations Research Articles

Angiotensin and biased analogs induce structurally distinct active conformations within a GPCR.

Biased agonists of G protein-coupled receptors (GPCRs) preferentially activate a subset of downstream signaling pathways. In this work, we present crystal structures of angiotensin II type 1 receptor (AT1R) (2.7 to 2.9 angstroms) bound to three ligands with divergent bias profiles: the balanced endogenous agonist angiotensin II (AngII) and two strongly β-arrestin-biased analogs. Compared with other ligands, AngII promotes more-substantial rearrangements not only at the bottom of the ligand-binding pocket but also in a key polar network in the receptor core, which forms a sodium-binding site in most GPCRs. Divergences from the family consensus in this region, which appears to act as a biased signaling switch, may predispose the AT1R and certain other GPCRs (such as chemokine receptors) to adopt conformations that are capable of activating β-arrestin but not heterotrimeric Gq protein signaling.

Choosing the drug to fit the protein

Structural Biology Many approved drugs bind to G protein–coupled receptors (GPCRs). A challenge in targeting GPCRs is that different ligands preferentially activate different signaling pathways. Two papers show how biased signaling arises for the angiotensin II type 1 receptor that couples to two signaling partners (G proteins and arrestins). Suomivuori et al. used large-scale atomistic simulations to show that coupling to the two pathways is through two distinct GPCR conformations and that extracellular ligands favor one or the other conformation. Wingler et al. present crystal structures of the same receptor bound to ligands with different bias profiles. These structures show conformational changes in and around the binding pocket that match those observed in simulations. This work could provide a framework for the rational design of drugs that are more effective and have fewer side effects. Science , this issue p. [881][1], p. [888][2] [1]: /lookup/doi/10.1126/science.aaz0326 [2]: /lookup/doi/10.1126/science.aay9813

Molecular mechanism of biased signaling in a prototypical G protein-coupled receptor.

Biased signaling, in which different ligands that bind to the same G protein-coupled receptor preferentially trigger distinct signaling pathways, holds great promise for the design of safer and more effective drugs. Its structural mechanism remains unclear, however, hampering efforts to design drugs with desired signaling profiles. Here, we use extensive atomic-level molecular dynamics simulations to determine how arrestin bias and G protein bias arise at the angiotensin II type 1 receptor. The receptor adopts two major signaling conformations, one of which couples almost exclusively to arrestin, whereas the other also couples effectively to a G protein. A long-range allosteric network allows ligands in the extracellular binding pocket to favor either of the two intracellular conformations. Guided by this computationally determined mechanism, we designed ligands with desired signaling profiles.

Nanoscale flaw tolerance behaviour of polycrystalline tetragonal zirconia nanopillars

Flaw tolerance behaviour of polycrystalline tetragonal zirconia nanopillars under compression is investigated by completing a series of large-scale atomistic simulations. Our simulation results show that the observed tetragonal to monoclinic phase transformation in zirconia does not necessarily nucleate around a pre-existing defect. A competing mechanism between grain boundary (GB)-induced and void-induced phase transformation is revealed. This work is the first direct atomistic simulation of flaw tolerance behavior in shape memory ceramics that offers a pseudo Griffith relationship between the strength, void size, and average grain size. The key finding is that the mechanical properties, particularly the strength, can become insensitive to a pre-existing defect in certain conditions depending on the average grain size and defect size. The obtained results provide new insight into the deformation mechanisms of defective polycrystalline tetragonal zirconia nanopillars.

Atomistic and finite element study of nanoindentation in pure aluminum

Nanoindentation is a useful technique to measure mechanical properties of a material such as the elastic modulus and hardness etc. In this paper, the effects of crystallographic orientation, indentation speed, indentation depth and indenter size has been studied for pure Aluminum (Al) using dislocation nucleation and propagation mechanism in atomistic simulation. The materials properties like hardness and reduced modulus are also calculated from the atomistic simulations. Nanoscale finite element (FE) simulations in Al are carried out using molecular dynamics tensile test data as input parameters and compared with atomistic results. The proposed methodology reduces the computational time and cost and reproduces the material properties with reasonable accuracy. The investigations of atomistic simulations include the load-displacement analysis, dislocation density and dislocation loops nucleation and propagation, von-Mises stress distribution and surface imprint. This study provides a pathway to obtain the materials properties for nanoscale materials without performing large scale atomistic simulation and can be applied for other mechanical properties such as fatigue, creep simulation of materials.

Mechanical properties of nanoporous metallic glasses: Insights from large-scale atomic simulations

While recent attention has been directed towards fabricating porous metallic glasses (MGs) with a wide range of pore sizes varying from nanometer to micrometer owing to their unique mechanical properties, there has been so far little or no atomic-level understanding of the deformation and failure mechanisms involved. Here we systematically investigate the mechanical response of nanoporous MGs under uniaxial tensile and compressive tests via large-scale molecular dynamics simulations. A scaling law is observed for the ultimate strength. Results show that nanoporous MGs fail by necking in tension. However, shear banding prevails when the ligaments possess a low slenderness ratio less than 2.0 and are inclined to the loading direction. Furthermore, the compressive strength value is found to be lower than that under tension due to the surface energy effect, which is contrary to the tension/compression asymmetry observed in monolithic MGs. Our study provides an atomic-level understanding of the fundamental failure mechanism in nanoporous MGs, which may offer new insights to the design and application of nanoporous MGs.

Correction: The effect of pulse duration on nanoparticle generation in pulsed laser ablation in liquids: insights from large-scale atomistic simulations.

Correction for 'The effect of pulse duration on nanoparticle generation in pulsed laser ablation in liquids: insights from large-scale atomistic simulations' by Cheng-Yu Shih et al., Phys. Chem. Chem. Phys., 2020, 22, 7077-7099, DOI: .

The effect of pulse duration on nanoparticle generation in pulsed laser ablation in liquids: insights from large-scale atomistic simulations.

The generation of colloidal solutions of chemically clean nanoparticles through pulsed laser ablation in liquids (PLAL) has evolved into a thriving research field that impacts industrial applications. The complexity and multiscale nature of PLAL make it difficult to untangle the various processes involved in the generation of nanoparticles and establish the dependence of nanoparticle yield and size distribution on the irradiation parameters. Large-scale atomistic simulations have yielded important insights into the fundamental mechanisms of ultrashort (femtoseconds to tens of picoseconds) PLAL and provided a plausible explanation of the origin of the experimentally observed bimodal nanoparticle size distributions. In this paper, we extend the atomistic simulations to short (hundreds of picoseconds to nanoseconds) laser pulses and focus our attention on the effect of the pulse duration on the mechanisms responsible for the generation of nanoparticles at the initial dynamic stage of laser ablation. Three distinct nanoparticle generation mechanisms operating at different stages of the ablation process and in different parts of the emerging cavitation bubble are identified in the simulations. These mechanisms are (1) the formation of a thin transient metal layer at the interface between the ablation plume and water environment followed by its decomposition into large molten nanoparticles, (2) the nucleation, growth, and rapid cooling/solidification of small nanoparticles at the very front of the emerging cavitation bubble, above the transient interfacial metal layer, and (3) the spinodal decomposition of a part of the ablation plume located below the transient interfacial layer, leading to the formation of a large population of nanoparticles growing in a high-temperature environment through inter-particle collisions and coalescence. The coexistence of the three distinct mechanisms of the nanoparticle formation at the initial stage of the ablation process can be related to the broad nanoparticle size distributions commonly observed in nanosecond PLAL experiments. The strong dependence of the nanoparticle cooling and solidification rates on the location within the low-density metal-water mixing region has important implications for the long-term evolution of the nanoparticle size distribution, as well as for the ability to quench the nanoparticle growth or dope them by adding surface-active agents or doping elements to the liquid environment.

Exploring the structure-property relationship of three-dimensional hexagonal boron nitride aerogels with gyroid surfaces.

Three-dimensional hexagonal boron nitride aerogels (hBNAGs) are novel porous materials with many promising applications such as energy storage, thermal insulation and sensing. However, the structure-property relationships of hBNAGs in complicated thermo-mechanical coupled environments are still not clear. In this study, we employed a binary phase-field crystal (PFC) model to construct the atomic structures of hBNAGs, upon which the mechanical and thermal behaviors of hBNAGs were systematically investigated using large-scale atomistic simulations. It is found that the hBNAG geometry and topological defects strongly affect the mechanical and thermal properties. For example, the Young's modulus and tensile strength follow the scaling laws of mass density with a power factor of about 1.4 and 1.2, respectively, indicating that the stretching and bending combine toward tensile deformation. In addition, cracks nucleate around the octagon defects, indicating that the tensile strength is also influenced by the topological defects. Under compression, complicated crumpled deformations and ridges in the entire region are observed and the compression strength follows the scaling law of mass density with a power factor above 2.0, which means that a large portion of the hBNAGs do not contribute to the compression load bearing. We find that hBNAGs have a very low thermal conductivity of about two orders of magnitude lower than that of a hBN sheet. Also, the thermal conductivity of hBNAGs increases with increasing mass density, which also follows a scaling law. The power of the scaling law is about 0.5, indicating that the thermal conductivity has a strong nonlinear dependence on the mass density. Our work provides a deep understanding of the structure-property relationships of hBNAGs, which is useful for the engineering applications of hBNAGs.

Exchange of water for sterol underlies sterol egress from a StARkin domain.

Previously we identified Lam/GramD1 proteins, a family of endoplasmic reticulum membrane proteins with sterol-binding StARkin domains that are implicated in intracellular sterol homeostasis. Here, we show how these proteins exchange sterol molecules with membranes. An aperture at one end of the StARkin domain enables sterol to enter/exit the binding pocket. Strikingly, the wall of the pocket is longitudinally fractured, exposing bound sterol to solvent. Large-scale atomistic molecular dynamics simulations reveal that sterol egress involves widening of the fracture, penetration of water into the cavity, and consequent destabilization of the bound sterol. The simulations identify polar residues along the fracture that are important for sterol release. Their replacement with alanine affects the ability of the StARkin domain to bind sterol, catalyze inter-vesicular sterol exchange and alleviate the nystatin-sensitivity of lam2Δ yeast cells. These data suggest an unprecedented, water-controlled mechanism of sterol discharge from a StARkin domain.

Ion Agglomeration and Transport in MgCl2-Based Electrolytes for Rechargeable Magnesium Batteries.

Magnesium halide salts are an exciting prospect as stable and high-performance electrolytes for rechargeable Mg batteries (RMBs). By nature of their complex equilibria, these salts exist in solution as a variety of electroactive species (EAS) in equilibrium with counterions such as AlCl4-. Here we investigated ion agglomeration and transport of several such EAS in MgCl2 salts dissolved in ethereal solvents under both equilibrium and operating conditions using large-scale atomistic simulations. We found that the solute morphology is strongly characterized by the presence of clusters and is governed by the solvation structures of EAS. Specifically, the isotropic solvation of Mg2+ results in the slow formation of a bulky cluster, compared with chainlike analogues observed in the Cl-containing EAS such as Mg2Cl3+, MgCl+, and Mg2Cl22+. We further illustrate these clusters can reduce the diffusivity of charge-carrying species in the MgCl2-based electrolyte by at least an order of magnitude. Our findings for cluster formation, morphology, and kinetics can provide useful insight into the electrochemical reactions at the anode-electrolyte interface in RMBs.

Hybrid neural network potential for multilayer graphene

Monolayer and multilayer graphene are promising materials for applications such as electronic devices, sensors, energy generation and storage, and medicine. In order to perform large-scale atomistic simulations of the mechanical and thermal behavior of graphene-based devices, accurate interatomic potentials are required. Here, we present an interatomic potential for multilayer graphene structures referred to as ``$\mathrm{hNN}\text{\ensuremath{-}}{\mathrm{Gr}}_{x}$.'' This hybrid potential employs a neural network to describe short-range interactions and a theoretically motivated analytical term to model long-range dispersion. The potential is trained against a large dataset of monolayer graphene, bilayer graphene, and graphite configurations obtained from ab initio total-energy calculations based on density functional theory (DFT). The potential provides accurate energy and forces for both intralayer and interlayer interactions, correctly reproducing DFT results for structural, energetic, and elastic properties such as the equilibrium layer spacing, interlayer binding energy, elastic moduli, and phonon dispersions to which it was not fit. The potential is used to study the effect of vacancies on thermal conductivity in monolayer graphene and interlayer friction in bilayer graphene. The potential is available through the openkim interatomic potential repository at https://openkim.org.

Assessment of hardening due to non-coherent precipitates in tungsten-rhenium alloys at the atomic scale

In metallurgical applications, precipitation strengthening is of great technological importance to engineer materials with the required strength. While precipitation hardening is essential for many applications involving operation at elevated temperatures, its subsequent embrittlement can be a showstopper for the overall performance of a component. In the nuclear industry, irradiation-induced/enhanced precipitation and the resulting embrittlement often limit the lifetime of components. In fusion applications, tungsten (W) based alloys are known to harden and embrittle as a result of irradiation-assisted transmutation to rhenium (Re) and its subsequent precipitation into non-coherent precipitates. Hence, a fundamental understanding of the interaction of dislocations with non-coherent precipitates is of great interest. In the present work, the interaction of dislocations with non-coherent Re-rich σ, χ and hcp phase precipitates embedded in a bcc W matrix is assessed. Large-scale atomistic simulations are performed to clarify the interaction mechanisms and derive the obstacle strength of the precipitates in the quasi-static limit. Thereby the impact of precipitate shape, size, interspacing and composition is assessed. Based on those results, an analytical model to predict precipitation hardening of σ, χ and hcp phase particles in bcc W is proposed and compared to available experimental data from mechanical tests on irradiated materials.

Structure and Dynamics of Spherical and Rodlike Alkyl Ethoxylate Surfactant Micelles Investigated Using NMR Relaxation and Atomistic Molecular Dynamics Simulations.

Predicting and controlling the properties of amphiphile aggregate mixtures require understanding the arrangements and dynamics of the constituent molecules. To explore these topics, we study molecular arrangements and dynamics in alkyl ethoxylate nonionic surfactant micelles by combining NMR relaxation measurements with large-scale atomistic molecular dynamics simulations. We calculate parameters that determine relaxation rates directly from simulated trajectories, without introducing specific functional forms to describe the dynamics. NMR relaxation rates, which depend on relative motions of interacting atom pairs, are influenced by wide distributions of dynamic time scales. We find that relative motions of neighboring atom pairs are rapid and liquidlike but are subject to structural constraints imposed by micelle morphology. Relative motions of distant atom pairs are slower than nearby atom pairs because changes in distances and angles are smaller when the moving atoms are further apart. Large numbers of atom pairs undergoing these slow relative motions contribute to predominantly negative cross-relaxation rates. For spherical micelles, but not for cylindrical micelles, cross-relaxation rates are positive only for surfactant tail atoms connected to the hydrophilic headgroup. This effect is related to the lower packing density of these atoms at the hydrophilic-hydrophobic boundary in spherical vs cylindrical arrangements, with correspondingly rapid and less constrained motion of atoms at the boundary.

Heterogeneous catalysis from structure to activity via SSW-NN method

Modern research on heterogeneous catalysis calls for new techniques and methods to resolve the active site structure and reaction intermediates at the atomic scale. Here, we overview our recent progress on large-scale atomistic simulation via potential energy surface (PES) global optimization based on neural network (NN) potential, focusing on methodology details and recent applications on catalysis. The combination of stochastic surface walking (SSW) global optimization and the NN method provides a convenient and automated way to generate the transferable and robust NN potential for global PES, which can be utilized to reveal new chemistry from the unknown region of PES with an affordable computational cost. The predictive power of SSW-NN is demonstrated in several examples, where the method is applied to explore the material crystal phases, to follow the surface structure evolution under high pressure hydrogen and to determine the ternary oxide phase diagram. The limitations and future directions to develop the SSW-NN method are also discussed.

An electrostatic spectral neighbor analysis potential for lithium nitride

Machine-learned interatomic potentials based on local environment descriptors represent a transformative leap over traditional potentials based on rigid functional forms in terms of prediction accuracy. However, a challenge in their application to ionic systems is the treatment of long-ranged electrostatics. Here, we present a highly accurate electrostatic Spectral Neighbor Analysis Potential (eSNAP) for ionic α-Li3N, a prototypical lithium superionic conductor of interest as a solid electrolyte or coating for rechargeable lithium-ion batteries. We show that the optimized eSNAP model substantially outperforms traditional Coulomb–Buckingham potential in the prediction of energies and forces, as well as various properties, such as lattice constants, elastic constants, and phonon dispersion curves. We also demonstrate the application of eSNAP in long-time, large-scale Li diffusion studies in Li3N, providing atomistic insights into measures of concerted ionic motion (e.g., the Haven ratio) and grain boundary diffusion. This work aims at providing an approach to developing quantum-accurate force fields for multi-component ionic systems under the SNAP formalism, enabling large-scale atomistic simulations for such systems.

Theoretical strength and rubber-like behaviour in micro-sized pyrolytic carbon.

The creation of materials with a combination of high strength, substantial deformability and ductility, large elastic limit and low density represents a long-standing challenge, because these properties are, in general, mutually exclusive. Using a combination of two-photon lithography and high-temperature pyrolysis, we have created micro-sized pyrolytic carbon with a tensile strength of 1.60 ± 0.55 GPa, a compressive strength approaching the theoretical limit of ~13.7 GPa, a substantial elastic limit of 20-30% and a low density of ~1.4 g cm-3. This corresponds to a specific compressive strength of 9.79 GPa cm3 g-1, a value that surpasses that of nearly all existing structural materials. Pillars with diameters below 2.3 μm exhibit rubber-like behaviour and sustain a compressive strain of ~50% without catastrophic failure; larger ones exhibit brittle fracture at a strain of ~20%. Large-scale atomistic simulations reveal that this combination of beneficial mechanical properties is enabled by the local deformation of 1 nm curled graphene fragments within the pyrolytic carbon microstructure, the interactions among neighbouring fragments and the presence of covalent carbon-carbon bonds.

Low-angle grain boundary structures and size effects of nickel nanolaminated structures

Recent experiments have demonstrated the fabrication of nickel nanolaminated structures with low-angle grain boundaries and that these nanolaminated structures exhibit an ultrahigh hardness of 6.4 GPa and excellent thermal stability. However, the detailed microstructure of the low-angle grain boundary in these nanolaminated structures and plastic deformation mechanisms underlying their ultrahigh hardness have remained elusive to date. Thus, we performed a series of large-scale atomistic simulations to explore the microstructures, thermal stability and energies of the low-angle grain boundary in nanolaminated nickel and to further mimic the plastic deformation of nanolaminated nanopillars. First, we examined the thermal stability of low-angle grain boundaries in nanolaminated structures with three typical textures observed in previous experiments, and we found that the {111}<110>-textured nanolaminated structure is the most stable and has a critical temperature of approximately 750 K for stability. The low-angle grain boundary in such nanolaminated structures consists of a periodic arrangement of three types of dislocations with Burgers vectors of 1/2[101], 1/3[11¯1] and 1/6[14¯1]. Our simulations also showed that the grain boundary energy of the low-angle grain boundary with misorientation of 5° is approximately 0.70 J/m2 and that the interaction energy between two low-angle grain boundaries follows a power law as the lamellar thickness, with an exponent of −1.14. We further simulated the uniaxial compression and tension of nanolaminated nanopillars with a texture of {111}<110> and different lamellar thicknesses. The simulation results showed that as the lamellar thickness decreases, both compressive and tensile yield stresses significantly decrease, while their flow stresses slightly increase. The size effect on yield stress is attributed to dislocation escape from the low-angle grain boundary due to some typical reactions of constituent dislocations, while the size effect on flow stress is related to a complex reaction and interaction of high-density dislocations. Our study provides a fundamental understanding of the grain boundary structure and plastic deformation in textured nanolaminated metals, which offers insights for the design of stronger nanolaminated structures.

Reactive Force Field for Simulations of the Pyrolysis of Polysiloxanes into Silicon Oxycarbide Ceramics

We provide a new reactive force field (ReaxFF) for simulations of silicon oxycarbide (SiCO) ceramics and of their syntheses from inorganic polymer precursors. The validity of the force field is extensively tested against experimental and computational thermochemical data. Its performance in simulation at elevated temperatures is gauged by the results of comprehensive ab initio molecular dynamics simulations. We apply the force field to the formation of amorphous SiCO in a simulated polymer pyrolysis. Modeling results are in good agreement with experimental observations and allow new insights into the formation of graphene segregations embedded in an amorphous oxycarbide matrix. The new ReaxFF for Si–C–O–H compounds enables large-scale and long-time atomistic simulations with unprecedented fidelity.

Balanced internal hydration discriminates substrate binding to respiratory complex I

Molecular recognition of the amphiphilic electron carrier ubiquinone (Q) by respiratory complexes is a fundamental part of electron transfer chains in mitochondria and bacteria. The primary respiratory complex I binds Q in a long and narrow protein chamber to catalyse its reduction. But, the binding mechanism and the role of chamber hydration in substrate selectivity and stability are unclear. Here, large-scale atomistic molecular dynamics simulations and estimated free energy profiles are used to characterize in detail the binding mechanism to complex I of Q with short and with long isoprenoid tails. A highly stable binding site with two different poses near the chamber exit and a secondary reactive site near the N2 iron-sulfur cluster are found which may lead to an alternative Q redox chemistry and help to explain complex I reactivity. The binding energetics depends mainly on polar interactions of the Q-head and on the counterbalanced hydration of Q-tail isoprenoid units and hydrophobic residues inside the protein chamber. Selectivity upon variation of tail length arises by shifting the hydration balance. This internal hydration mechanism may have implications for binding of amphiphilic molecules to cavities in other membrane proteins.