Thermal and pressure-induced martensitic phase transformations in a Ni–Al alloy modelled by Sutton–Chen embedded atom method

The Ni–Al alloys which exhibit the thermoelastic martensitic phase transformations in the composition range from 60 to 65 atomic percentage (at.%) of Ni are widely used in the high technology applications. In this study, both thermal and pressure-induced phase transformations in Ni-37.5 at.%Al alloy model were investigated by a molecular dynamics (MD) method. Physical interactions between atoms in the alloy system were modelled using the Sutton–Chen version of the embedded atom method based on many-body interactions. The potential parameters for cross interactions between Ni and Al atoms were estimated by optimising the results obtained from the MD simulations, taking into account the experimental data including the crystal lattice properties of the model alloy in high temperature phase.     

A molecular dynamics study on intermediate structures during transition from amorphous to crystalline state

Molecular dynamics (MD) simulations are carried out for model aluminium with 500, 864, 1372 and 2048 atoms interacting with Sutton-Chen version of embedded atom method (SCEAM) based on many body interactions. The systems equilibrated in an FCC structure have, first, been melted and then solidified with specifically selected single cooling rate which forms unstable amorphous state in the system. The local structures of the system have been analysed by bond orientational order parameters to distinguish the simple structures in the systems. The radial distribution functions (RDF) and atomic coordinates have also been analysed for determining the local structural properties. It has been observed that the phase sequences of the systems, except for those of the 2048 atoms, are FCC → Liquid → Amorphous → Mixed Crystal. Types of the crystals in the mixed state depend on the number of the atoms in the system. The final phase of the system with 2048 atoms is amorphous state.     

Multiangular method for analysing molecular geometry from nuclear Overhauser effect results

A multiangular method, as an extension of a triangular method, has been developed in order to analyse the local conformation of a molecule in an atomic resolution from nuclear Overhauser effect results. When there is a rigid part in the molecule, and the nuclear Overhauser effect signals are observed between several spins attributed to the rigid part of the molecule and the target spin to be analysed, the geometrical probability density of the target spin can be found by the multiangulation method, using distances between spin pairs. The spin density is illustrated by a set of isograms similar to electron density maps from X-ray crystallographic analyses. The molecular model building is performed based upon the isograms. An application to the conformation analysis of transferred nuclear magnetic resonance results of NAD⁺, which binds to lactose dehydrogenace from Thermus caldophilus GK24, is described.     

On contribution of known atomic partial charges of protein backbone in electrostatic potential density maps

Partial charges of atoms in a molecule and electrostatic potential (ESP) density for that molecule are known to bear a strong correlation. In order to generate a set of point‐field force field parameters for molecular dynamics, Kollman and coworkers have extracted atomic partial charges for each of all 20 amino acids using restrained partial charge‐fitting procedures from theoretical ESP density obtained from condensed‐state quantum mechanics. The magnitude of atomic partial charges for neutral peptide backbone they have obtained is similar to that of partial atomic charges for ionized carboxylate side chain atoms. In this study, the effect of these known atomic partial charges on ESP is examined using computer simulations and compared with the experimental ESP density recently obtained for proteins using electron microscopy. It is found that the observed ESP density maps are most consistent with the simulations that include atomic partial charges of protein backbone. Therefore, atomic partial charges are integral part of atomic properties in protein molecules and should be included in model refinement.     

Solvating atomic level fine-grained proteins in supra-molecular level coarse-grained water for molecular dynamics simulations

Simulation of the dynamics of a protein in aqueous solution using an atomic model for both the protein and the many water molecules is still computationally extremely demanding considering the time scale of protein motions. The use of supra-atomic or supra-molecular coarse-grained (CG) models may enhance the computational efficiency, but inevitably at the cost of reduced accuracy. Coarse-graining solvent degrees of freedom is likely to yield a favourable balance between reduced accuracy and enhanced computational speed. Here, the use of a supra-molecular coarse-grained water model that largely preserves the thermodynamic and dielectric properties of atomic level fine-grained (FG) water in molecular dynamics simulations of an atomic model for four proteins is investigated. The results of using an FG, a CG, an implicit, or a vacuum solvent environment of the four proteins are compared, and for hen egg-white lysozyme a comparison to NMR data is made. The mixed-grained simulations do not show large differences compared to the FG atomic level simulations, apart from an increased tendency to form hydrogen bonds between long side chains, which is due to the reduced ability of the supra-molecular CG beads that represent five FG water molecules to make solvent-protein hydrogen bonds. But, the mixed-grained simulations are at least an order of magnitude faster than the atomic level ones.     

Deriving theoretical phase locking values of a coupled cortico-thalamic neural mass model using center manifold reduction

Cognitive functions such as sensory processing and memory processes lead to phase synchronization in the electroencephalogram or local field potential between different brain regions. There are a lot of computational researches deriving phase locking values (PLVs), which are an index of phase synchronization intensity, from neural models. However, these researches derive PLVs numerically. To the best of our knowledge, there have been no reports on the derivation of a theoretical PLV. In this study, we propose an analytical method for deriving theoretical PLVs from a cortico-thalamic neural mass model described by a delay differential equation. First, the model for generating neural signals is transformed into a normal form of the Hopf bifurcation using center manifold reduction. Second, the normal form is transformed into a phase model that is suitable for analyzing synchronization phenomena. Third, the Fokker–Planck equation of the phase model is derived and the phase difference distribution is obtained. Finally, the PLVs are calculated from the stationary distribution of the phase difference. The validity of the proposed method is confirmed via numerical simulations. Furthermore, we apply the proposed method to a working memory process, and discuss the neurophysiological basis behind the phase synchronization phenomenon. The results demonstrate the importance of decreasing the intensity of independent noise during the working memory process. The proposed method will be of great use in various experimental studies and simulations relevant to phase synchronization, because it enables the effect of neurophysiological changes on PLVs to be analyzed from a mathematical perspective.     

Improving the iterative Linear Interaction Energy approach using automated recognition of configurational transitions

Recently an iterative method was proposed to enhance the accuracy and efficiency of ligand-protein binding affinity prediction through linear interaction energy (LIE) theory. For ligand binding to flexible Cytochrome P450s (CYPs), this method was shown to decrease the root-mean-square error and standard deviation of error prediction by combining interaction energies of simulations starting from different conformations. Thereby, different parts of protein-ligand conformational space are sampled in parallel simulations. The iterative LIE framework relies on the assumption that separate simulations explore different local parts of phase space, and do not show transitions to other parts of configurational space that are already covered in parallel simulations. In this work, a method is proposed to (automatically) detect such transitions during the simulations that are performed to construct LIE models and to predict binding affinities. Using noise-canceling techniques and splines to fit time series of the raw data for the interaction energies, transitions during simulation between different parts of phase space are identified. Boolean selection criteria are then applied to determine which parts of the interaction energy trajectories are to be used as input for the LIE calculations. Here we show that this filtering approach benefits the predictive quality of our previous CYP 2D6-aryloxypropanolamine LIE model. In addition, an analysis is performed of the gain in computational efficiency that can be obtained from monitoring simulations using the proposed filtering method and by prematurely terminating simulations accordingly.     

Temperature-dependent molecular dynamics and restrained X-ray refinement simulations of a Z-DNA hexamer

Molecular dynamics simulations of the Z-DNA hexamer 5BrdC-dG-5BrdC-dG-5BrdC-dG were performed at several temperatures between 100 K and 300 K. Above 250 K, a strong sequence-dependent flexibility in the nucleic acid is observed, with the guanine sugar and the phosphate of GpC sequences much more mobile than the cytosine sugar and phosphate of CpG sequences. At 300 K, the hexamer is in dynamic equilibrium between several Z forms, including the crystallographically determined ZI and ZII forms. The local base-pair geometry, however, is not very variable, except for the roll of the base-pairs. The hexamer molecular dynamics trajectories have been used to test the restrained parameter crystallographic refinement model for nucleic acids. X-ray diffraction intensities corresponding to observed diffraction data were computed. The average structures obtained from the simulations were then refined against the calculated intensities, using a restrained least-squares program developed for nucleic acids in order to analyse the effects of the refinement model on the derived quantities. In general, the temperature dependence of the atomic fluctuations determined directly from the refined Debye-Waller factors is in reasonably good agreement with the results obtained by calculating the atomic fluctuations directly from the Z-DNA molecular dynamics trajectories. The agreement is best for refinement of temperature factors without restraints. At the highest temperature studied (300 K), the effect of the refinement on the most mobile atoms (phosphates) is to significantly reduce the mean-square atomic fluctuations estimated from the refined Debye-Waller factors below the actual values (less than (delta r)2 greater than congruent to 0.5 A2). Analysis of the temperature-dependence of the mean-square atomic fluctuations provides information concerning the conformational potential within which the atoms move. The calculated temperature-dependence and anharmonicity of the Z-DNA helix are compared with the results observed for proteins. The average structures from the simulations were refined against the experimental X-ray intensities. It is found that low-temperature molecular dynamics simulations provide a useful tool for optimizing the refinement of X-ray structures.     

Long time dynamics of Met-enkephalin: comparison of explicit and implicit solvent models

Met-enkephalin is one of the smallest opiate peptides. Yet, its dynamical structure and receptor docking mechanism are still not well understood. The conformational dynamics of this neuron peptide in liquid water are studied here by using all-atom molecular dynamics (MD) and implicit water Langevin dynamics (LD) simulations with AMBER potential functions and the three-site transferable intermolecular potential (TIP3P) model for water. To achieve the same simulation length in physical time, the full MD simulations require 200 times as much CPU time as the implicit water LD simulations. The solvent hydrophobicity and dielectric behavior are treated in the implicit solvent LD simulations by using a macroscopic solvation potential, a single dielectric constant, and atomic friction coefficients computed using the accessible surface area method with the TIP3P model water viscosity as determined here from MD simulations for pure TIP3P water. Both the local and the global dynamics obtained from the implicit solvent LD simulations agree very well with those from the explicit solvent MD simulations. The simulations provide insights into the conformational restrictions that are associated with the bioactivity of the opiate peptide dermorphin for the delta-receptor.     

Combined effects of pulsatile flow and dynamic curvature on wall shear stress in a coronary artery bifurcation model

A three-dimensional model with simplified geometry for the branched coronary artery is presented. The bifurcation is defined by an analytical intersection of two cylindrical tubes lying on a sphere that represents an idealized heart surface. The model takes into account the repetitive variation of curvature and motion to which the vessel is subject during each cardiac cycle, and also includes the phase difference between arterial motion and blood flowrate, which may be nonzero for patients with pathologies such as aortic regurgitation. An arbitrary Lagrangian Eulerian (ALE) formulation of the unsteady, incompressible, three-dimensional Navier-Stokes equations is employed to solve for the flow field, and numerical simulations are performed using the spectral/hp element method. The results indicate that the combined effect of pulsatile inflow and dynamic geometry depends strongly on the aforementioned phase difference. Specifically, the main findings of this work show that the time-variation of flowrate ratio between the two branches is minimal (less than 5%) for the simulation with phase difference angle equal to 90 degrees, and maximal (51%) for 270 degrees. In two flow pulsatile simulation cases for fixed geometry and dynamic geometry with phase angle 270 degrees, there is a local minimum of the normalized wall shear rate amplitude in the vicinity of the bifurcation, while in other simulations a local maximum is observed.     

Probing conformational disorder in neurotensin by two-dimensional solid-state NMR and comparison to molecular dynamics simulations

An approach is introduced to characterize conformational ensembles of intrinsically unstructured peptides on the atomic level using two-dimensional solid-state NMR data and their combination with molecular dynamics simulations. For neurotensin, a peptide that binds with high affinity to a G-protein coupled receptor, this method permits the investigation of the changes in conformational preferences of a neurotransmitter transferred from a frozen aqueous solution via a lipid model phase to the receptor-bound form. The results speak against a conformational pre-organization of the ligand in detergents in which the receptor has been shown to be functional. Further extensions to the study of protein folding are possible.     

Reparameterization of all-atom dipalmitoylphosphatidylcholine lipid parameters enables simulation of fluid bilayers at zero tension

Molecular dynamics simulations of dipalmitoylphosphatidylcholine (DPPC) lipid bilayers using the CHARMM27 force field in the tensionless isothermal-isobaric (NPT) ensemble give highly ordered, gel-like bilayers with an area per lipid of approximately 48 A(2). To obtain fluid (L(alpha)) phase properties of DPPC bilayers represented by the CHARMM energy function in this ensemble, we reparameterized the atomic partial charges in the lipid headgroup and upper parts of the acyl chains. The new charges were determined from the electron structure using both the Mulliken method and the restricted electrostatic potential fitting method. We tested the derived charges in molecular dynamics simulations of a fully hydrated DPPC bilayer. Only the simulation with the new restricted electrostatic potential charges shows significant improvements compared with simulations using the original CHARMM27 force field resulting in an area per lipid of 60.4 +/- 0.1 A(2). Compared to the 48 A(2), the new value of 60.4 A(2) is in fair agreement with the experimental value of 64 A(2). In addition, the simulated order parameter profile and electron density profile are in satisfactory agreement with experimental data. Thus, the biologically more interesting fluid phase of DPPC bilayers can now be simulated in all-atom simulations in the NPT ensemble by employing our modified CHARMM27 force field.     

Contribution of muscle short-range stiffness to initial changes in joint kinetics and kinematics during perturbations to standing balance: A simulation study

Simulating realistic musculoskeletal dynamics is critical to understanding neural control of muscle activity evoked in sensorimotor feedback responses that have inherent neural transmission delays. Thus, the initial mechanical response of muscles to perturbations in the absence of any change in muscle activity determines which corrective neural responses are required to stabilize body posture. Muscle short-range stiffness, a history-dependent property of muscle that causes a rapid and transient rise in muscle force upon stretch, likely affects musculoskeletal dynamics in the initial mechanical response to perturbations. Here we identified the contributions of short-range stiffness to joint torques and angles in the initial mechanical response to support surface translations using dynamic simulation. We developed a dynamic model of muscle short-range stiffness to augment a Hill-type muscle model. Our simulations show that short-range stiffness can provide stability against external perturbations during the neuromechanical response delay. Assuming constant muscle activation during the initial mechanical response, including muscle short-range stiffness was necessary to account for the rapid rise in experimental sagittal plane knee and hip joint torques that occurs simultaneously with very small changes in joint angles and reduced root mean square errors between simulated and experimental torques by 56% and 47%, respectively. Moreover, forward simulations lacking short-range stiffness produced unreasonably large joint angle changes during the initial response. Using muscle models accounting for short-range stiffness along with other aspects of history-dependent muscle dynamics may be important to advance our ability to simulate inherently unstable human movements based on principles of neural control and biomechanics.     

Ion-induced alterations of the local hydration environment elucidate Hofmeister effect in a simple classical model of Trp-cage miniprotein

Protein stability is known to be influenced by the presence of Hofmeister active ions in the solution. In addition to direct ion-protein interactions, this influence manifests through the local alterations of the interfacial water structure induced by the anions and cations present in this region. In our earlier works it was pointed out that the effects of Hofmeister active salts on the stability of Trp-cage miniprotein can be modeled qualitatively using non-polarizable force fields. These simulations reproduced the structure-stabilization and structure-destabilization effects of selected kosmotropic and chaotropic salts, respectively. In the present study we use the same model system to elucidate atomic processes behind the chaotropic destabilization and kosmotropic stabilization of the miniprotein. We focus on changes of the local hydration environment of the miniprotein upon addition of NaClO₄ and NaF salts to the solution. The process is separated into two parts. In the first, ‘promotion’ phase, the protein structure is fixed, and the local hydration properties induced by the simultaneous presence of protein and ions are investigated, with a special focus on the interaction of Hofmeister active anions with the charged and polar sites. In the second, ‘rearrangement’ phase we follow changes of the hydration of ions and the protein, accompanying the conformational relaxation of the protein. We identify significant factors of an enthalpic and entropic nature behind the ion-induced free energy changes of the protein-water system, and also propose a possible atomic mechanism consistent with the Collins’s rule, for the chaotropic destabilization and kosmotropic stabilization of protein conformation.     

Brownian Dynamics Computer Simulations of Quenched Lennard-Jones-like Fluids: I Morphology and Local Structural Evolution

Abstract

The structural characteristics during phase separation of a model colloidal system were investigated using Brownian dynamics simulation. The structures that formed were analysed using the radial distribution function and structure factor in separate time periods after the quench. The data were interpreted in terms of scale-invariancy and density inhomogeneities. The systems, which consisted of a gas-like phase and dense liquid or solid-like regions, developed with a highly interconnected morphology during the simulations. The aggregate morphology was sensitive to the range of the attractive part of the potential and the position in the phase diagram after the quench. The long-range 12:6 potential induced compact structures with thick filaments, whereas the systems generated using the shorter-ranged 24:12 and 36:18 potentials persisted in a more diffuse network and also evolved more slowly with time. The fractal dimensions were quite high, typically close to 3. The 24:12 and 36:18 potential systems developed regions of local crystalline order which formed contemporaneously with the more global morphological changes. In contrast, at low temperatures the particles of the longer-range 12:6 potential became trapped in glass-like states during the course of the morphological changes in the system. The value of the characteristic lengthscale with time exponent, α, was found to be dependent on the temperature, density and interaction potential and therefore cannot be described as ‘universal’.     

A tool for the morphological analysis of mixtures of lipids and water in computer simulations

When analyzing computer simulations of mixtures of lipids and water, the questions to be answered are often of a morphological nature. They can deal with global properties, like the kind of phase that is adopted or the presence or absence of certain key features like a pore or stalk, or with local properties, like the local curvature present at a particular part of the lipid/water interface. While in principle all of the information relating to the global and local morphological properties of a system can be obtained from the set of atomic coordinates generated by a computer simulation, the extraction of this information is a tedious task that usually involves using a visualization program and performing the analysis by eye. Here we present a tool that employs the technique of morphological image analysis (MIA) to automatically extract the global morphology—as given by Minkowski functionals—from a set of atomic coordinates, and creates an image of the system onto which the local curvatures are mapped as a color code.     

Investigations of Nematic-Isotropic Transition by Means of Constant Pressure Molecular Dynamics Simulations

Abstract

Constant pressure molecular dynamics simulations, which secure the system to be under hydrostatic pressure, are used to simulate the behavior of liquid crystals consisting of anisotropic molecules with both translational and orientational freedom. In order to investigate to what extent can the properties known to real liquid crystalline phases be explained by the anisotropy of the shape of the molecules alone, the molecular dynamic (MD) simulation uses purely repulsive short-range pair potentials representing soft spherocylinders. A clear change in the microscopic as well as the macroscopic physical properties are observed near the phase transition from nematic liquid crystal to isotropic liquid.     

Anisotropic atomic motions in high-resolution protein crystallography molecular dynamics simulations

Molecular dynamics (MD) simulations using empirical force fields are popular for the study of proteins. In this work, we compare anisotropic atomic fluctuations in nanosecond-timescale MD simulations with those observed in an ultra-high-resolution crystal structure of crambin. In order to make our comparisons, we have developed a compact graphical technique for assessing agreement between spatial atomic distributions determined by MD simulations and observed anisotropic temperature factors.     

Molecular properties of a bent-core nematic liquid crystal A131 by multi-level theory simulations

ABSTRACT

Multi-level theory simulations have been performed to model a number of important molecular properties of a bent-core nematic liquid crystal (LC) A131. These important properties include molecular conformations, molecular Raman spectra, differential polarisability ratios, molecular crystals packing, atomic LC structures, order parameters, and Raman depolarisation spectra. The simulations contain four theory levels, involving molecular quantum chemistry, molecular crystal packing, super cell density functional based tight binding optimisation, and super cell molecular dynamics calculations. To heat initial optimised super cell structures, molecular dynamics simulations reveal phase transitions to uniaxial and biaxial nematic phases from molecular crystals. LC atomic structures result in direct calculations on order parameters, which can be further applied to computations on Raman depolarisation spectra with differential polarisability ratios, obtained in the molecular quantum chemistry theory level. The good agreement of simulated Raman depolarisation spectra with the experiment provides a detailed analysis on the unusually low values of experimental uniaxial order parameters.     

Kinetics and mechanism of the barotropic lamellar gel/lamellar liquid crystal phase transition in fully hydrated dihexadecylphosphatidylethanolamine: a time-resolved x-ray diffraction study using pressure jump.

The kinetics and mechanism of the barotropic lamellar gel (L beta')/lamellar liquid crystal (L alpha) phase transition in fully hydrated 1,2-dihexadecyl-sn-glycero-3-phosphoethanolamine (DHPE) has been studied using time-resolved x-ray diffraction (TRXRD). The phase transition was induced by pressure jumps of varying amplitudes in both the pressurization and depressurization directions at controlled temperature (78 degrees C). Both low- and wide-angle diffracted x rays were recorded simultaneously in live time using an x-ray-sensitive image intensifier coupled to a CCD camera and Super-VHS videotape recorder. Such an arrangement allowed for the direct and quantitative characterization of the long- (lamellar repeat spacing) and short-range order (chain packing) during a kinetic experiment. The image-processed live-time x-ray diffraction data were fitted using a nonlinear least-squares model, and the parameters of the fits were monitored continuously throughout the transition. The pressure-induced transitions from the L alpha to the L beta' phase and from the L beta' to the L alpha phase was two-state (no formation of intermediates apparent during the transition) to within the sensitivity limits of the method. The corresponding transit time (the time during which both phases coexist) associated with the long- and short-range order of the pressurization-induced L alpha-to-L beta' phase transition decreased to a limiting value of approximately 50 ms with increasing pressure jump amplitude. This limiting value was close to the response time of the detector/recording system. Thus, the intrinsic transit time of this transition in fully hydrated DHPE at 78 degrees C was less than or equal to 50 ms. In contrast, the depressurization-induced L beta'-to-L alpha phase transition was slower, taking approximately 1 s to complete, and occurred with no obvious dependence of the transit time on pressure jump amplitude. In the depressurization jump experiment, the lipid responded rapidly to the pressure jump in the L beta' phase up to the rate-determining L beta'-to-L alpha transition. Such behavior was examined carefully, as it could complicate the interpretation of phase transition kinetic measurements.