An exa-scale high-performance molecular dynamics simulation program: MODYLAS.

A new version of the highly parallelized general-purpose molecular dynamics (MD) simulation program MODYLAS with high performance on the Fugaku computer was developed. A benchmark test using Fugaku indicated highly efficient communication, single instruction, multiple data (SIMD) processing, and on-cache arithmetic operations. The system's performance deteriorated only slightly, even under high parallelization.

A hybrid approach to study large conformational transitions of biomolecules from single particle XFEL diffraction data.

X-ray free-electron laser (XFEL) is the latest generation of the X-ray source that could become an invaluable technique in structural biology. XFEL has ultrashort pulse duration, extreme peak brilliance, and high spatial coherence, which could enable the observation of the biological molecules in near nature state at room temperature without crystallization. However, for biological systems, due to their low diffraction power and complexity of sample delivery, experiments and data analysis are not straightforward, making it extremely challenging to reconstruct three-dimensional (3D) structures from single particle XFEL data.

Prediction of self-diffusion coefficients of chemically diverse pure liquids by all-atom molecular dynamics simulations.

Molecular self-diffusion coefficients underlie various kinetic properties of the liquids involved in chemistry, physics, and pharmaceutics. In this study, 547 self-diffusion coefficients are calculated based on all-atom molecular dynamics (MD) simulations of 152 diverse pure liquids at various temperatures employing the OPLS4 force field. The calculated coefficients are compared with experimental data (424 extracted from the literature and 123 newly measured by pulsed-field gradient nuclear magnetic resonance).

Global diffusion of hydrogen molecules in the heterogeneous structure of polymer electrolytes for fuel cells: Dynamic Monte Carlo combined with molecular dynamics calculations.

Using our recently developed dynamic Monte Carlo (MC) method [Nagai et al., J. Chem.

Dynamic Monte Carlo calculation generating particle trajectories that satisfy the diffusion equation for heterogeneous systems with a position-dependent diffusion coefficient and free energy.

A series of new Monte Carlo (MC) transition probabilities was investigated that could produce molecular trajectories statistically satisfying the diffusion equation with a position-dependent diffusion coefficient and potential energy. The MC trajectories were compared with the numerical solution of the diffusion equation by calculating the time evolution of the probability distribution and the mean first passage time, which exhibited excellent agreement. The method is powerful when investigating, for example, the long-distance and long-time global transportation of a molecule in heterogeneous systems by coarse-graining them into one-particle diffusive molecular motion with a position-dependent diffusion coefficient and free energy.

Three-dimensional free-energy landscape of hydrogen and oxygen molecules in polymer electrolyte membranes: Insight into diffusion paths.

Polymer electrolyte membranes, for example, the Nafion™ membranes, used in the fuel cells are responsible for separating reactive gas molecules as well as for the efficient exchange of protons. Although control of the permeation of the gases is important to enhance the fuel cell performance, the mechanism by which hydrogen and oxygen molecules permeate through the membranes remains unclear. To clarify the mechanism, we investigated the three-dimensional free-energy landscape of hydrogen and oxygen molecules in Nafion membranes with various water contents focusing on relevant diffusion paths.

Momentum removal to obtain the position-dependent diffusion constant in constrained molecular dynamics simulation.

The position-dependent diffusion coefficient along with free energy profile are important parameters needed to study mass transport in heterogeneous systems such as biological and polymer membranes, and molecular dynamics (MD) calculation is a popular tool to obtain them. Among many methodologies, the Marrink-Berendsen (MB) method is often employed to calculate the position-dependent diffusion coefficient, in which the autocorrelation function of the force on a fixed molecule is related to the friction on the molecule. However, the diffusion coefficient is shown to be affected by the period of the removal of the center-of-mass velocity, , which is necessary when performing MD calculations using the Ewald method for Coulombic interaction.

Position-Dependent Diffusion Constant of Molecules in Heterogeneous Systems as Evaluated by the Local Mean Squared Displacement.

The authors propose a novel method to evaluate the position-dependent diffusion constant by analyzing unperturbed segments of a trajectory determined by the additional flat-bottom potential. The accuracy of this novel method is first established by studying homogeneous systems, where the reference value can be obtained by the Einstein relation. The applicability of this new method to heterogeneous systems is then demonstrated by studying a hydrophobic solute near a hydrophobic wall.

Exploring the impact of proteins on the line tension of a phase-separating ternary lipid mixture.

The separation of lipid mixtures into thermodynamically stable phase-separated domains is dependent on lipid composition, temperature, and system size. Using molecular dynamics simulations, the line tension between thermodynamically stable lipid domains formed from ternary mixtures of di-C16:0 PC:di-C18:2 PC:cholesterol at 40:40:20 mol. % ratio was investigated via two theoretical approaches.

Cryo-Cooling Effect on DHFR Crystal Studied by Replica-Exchange Molecular Dynamics Simulations.

Cryo-cooling is routinely performed before x-ray diffraction image collection to reduce the damage to crystals due to ionizing radiation. It has been suggested that although backbone structures are usually very similar between room temperature and cryo-temperature, cryo-cooling may hamper biologically relevant dynamics. In this study, the crystal of Escherichia coli dihydrofolate reductase is studied with replica-exchange molecular dynamics simulation, and the results are compared with the crystal structure determined at cryo-temperature and room temperature with the time-averaged ensemble method.

Gaussian mixture model for coarse-grained modeling from XFEL.

We explore the advantage of Gaussian mixture model (GMM) for interpretation of single particle diffraction patterns from X-ray free electron laser (XFEL) experiments. GMM approximates a biomolecular shape by the superposition of Gaussian distributions. As the Fourier transformation of GMM can be quickly performed, we can efficiently simulate XFEL diffraction patterns from approximated structure models.

Role of Computational Methods in Going beyond X-ray Crystallography to Explore Protein Structure and Dynamics.

Protein structural biology came a long way since the determination of the first three-dimensional structure of myoglobin about six decades ago. Across this period, X-ray crystallography was the most important experimental method for gaining atomic-resolution insight into protein structures. However, as the role of dynamics gained importance in the function of proteins, the limitations of X-ray crystallography in not being able to capture dynamics came to the forefront.

Critical size dependence of domain formation observed in coarse-grained simulations of bilayers composed of ternary lipid mixtures.

Model cellular membranes are known to form micro- and macroscale lipid domains dependent on molecular composition. The formation of macroscopic lipid domains by lipid mixtures has been the subject of many simulation investigations. We present a critical study of system size impact on lipid domain phase separation into liquid-ordered and liquid-disordered macroscale domains in ternary lipid mixtures.

On the use of mass scaling for stable and efficient simulated tempering with molecular dynamics.

Simulated tempering (ST) is a generalized-ensemble algorithm that employs trajectories exploring a range of temperatures to effectively sample rugged energy landscapes. When implemented using the molecular dynamics method, ST can require the use of short time steps for ensuring the stability of trajectories at high temperatures. To address this shortcoming, a mass-scaling ST (MSST) method is presented in which the particle mass is scaled in proportion to the temperature.

Mass-scaling replica-exchange molecular dynamics optimizes computational resources with simpler algorithm.

We develop a novel method of replica-exchange molecular dynamics (REMD) simulation, mass-scaling REMD (MSREMD) method, which improves numerical stability of simulations. In addition, the MSREMD method can also simplify a replica-exchange routine by eliminating velocity scaling. As a pilot system, a Lennard-Jones fluid is simulated with the new method.

Simulated tempering and magnetizing: application of two-dimensional simulated tempering to the two-dimensional Ising model and its crossover.

We have performed two-dimensional simulated tempering (ST) simulations of the two-dimensional Ising model with different lattice sizes in order to investigate the two-dimensional ST's applicability to dealing with phase transitions and study the crossover of critical scaling behavior. The external field, as well as the temperature, was treated as a dynamical variable updated during the simulations. Thus this simulation can be referred to as simulated tempering and magnetizing (STM).

Synchronization of circadian oscillation of phosphorylation level of KaiC in vitro.

In recent experimental reports, robust circadian oscillation of the phosphorylation level of KaiC has been reconstituted by incubating three cyanobacterial proteins, KaiA, KaiB, and KaiC, with ATP in vitro. This reconstitution indicates that protein-protein interactions and the associated ATP hydrolysis suffice to generate the oscillation, and suggests that the rhythm arising from this protein-based system is the circadian clock pacemaker in cyanobacteria. The mechanism of this reconstituted oscillation, however, remains elusive.