Kazutomo Kawaguchi

MODYLAS: A Highly Parallelized General-Purpose Molecular Dynamics Simulation Program for Large-Scale Systems with Long-Range Forces Calculated by Fast Multipole Method (FMM) and Highly Scalable Fine-Grained New Parallel Processing Algorithms

Our new molecular dynamics (MD) simulation program, MODYLAS, is a general-purpose program appropriate for very large physical, chemical, and biological systems. It is equipped with most standard MD techniques. Long-range forces are evaluated rigorously by the fast multipole method (FMM) without using the fast Fourier transform (FFT). Several new methods have also been developed for extremely fine-grained parallelism of the MD calculation. The virtually buffering-free methods for communications and arithmetic operations, the minimal communication latency algorithm, and the parallel bucket-relay communication algorithm for the upper-level multipole moments in the FMM realize excellent scalability. The methods for blockwise arithmetic operations avoid data reload, attaining very small cache miss rates. Benchmark tests for MODYLAS using 65 536 nodes of the K-computer showed that the overall calculation time per MD step including communications is as short as about 5 ms for a 10 million-atom system; that is, 35 ns of simulation time can be computed per day. The program enables investigations of large-scale real systems such as viruses, liposomes, assemblies of proteins and micelles, and polymers.

Spectral Tuning of Photoactive Yellow Protein

We report a theoretical study on the optical properties of a small, water‐soluble photosensory receptor, photoactive yellow protein (PYP). A hierarchical ab initio molecular orbital calculation accurately evaluated the optical absorption maximum of the wild‐type, as well as the λmax values of 12 mutants. Electronic excitation of the chromophore directly affects the electronic state of nearby atoms in the protein environment. This effect is explicitly considered in the present study. Furthermore, the spectral tuning mechanism of PYP was investigated at the atomic level.

A simple coarse-grained model for interacting protein complex

ABSTRACT We present a simple coarse-grained model in which each amino acid residue is represented by one coarse-grained particle for interacting protein complex. In order to determine the coarse-grained potential function of the interaction between amino acid residues, free energy profile as a function of the distance between amino acid side chains is investigated by using all-atom molecular dynamics simulations with thermodynamic integration method. The Langevin dynamics simulation with Gō-like model and our coarse-grained model reproduces homotetramer complex structure of GCN4-pLI and shows that interaction between hydrophobic amino acid residues promote the association of GCN4-pLI monomers. GRAPHICAL ABSTRACT

The Potentials of the Atoms around Mg 2+ in the H-ras GTP and GDP Complexes

We have studied the quantum state around the Mg2+ ion in the H-ras GTP and H-ras GDP complexes in order to understand the hydrolysis of GTP to GDP in the H-ras complex, which plays a key role in overcoming human cancer. We calculated the force fields and atomic charges around the Mg2+ ion in the H-ras GTP and H-ras GDP complexes at the B3LYP level, using a basis functional set 6-31G**. The calculations were performed in the subsystem consisting of the bases or the molecules containing the oxygen having a coordinate bond to the Mg2+ ion. They showed that the oxygen atoms in both GTP and GDP bind tightly to the Mg2+ ion, although the oxygen atoms in H2O bind loosely. We have also performed MD simulations of the H-ras GTP and H-ras GDP complexes in solution, using these potential parameters. We showed that the structure differences between H-ras GTP and H-ras GDP are found mainly in loop 2 and loop 4.

Molecular dynamics studies of Hsp90 with ADP: Protein-ligand binding dynamics

Ligand binding to a protein molecule plays a key role in the function of many proteins. We performed all-atom model molecular dynamics (MD) simulations of the N-terminal domain of human Hsp90 in complex with ADP, and calculated a free energy profile for ligand binding with thermodynamic integration method. The free energy profile as a function of the distance between the centers of mass of the N-terminal domain of Hsp90 and ADP was calculated using the results of the binding-distance constrained MD simulations. The free energy profile was fit to a harmonic oscillator. We obtained spring constant k = 3.84kJ/mol⋅nm2 = 9.17×10−1kcal/mol⋅A2. This result indicates that the dynamics of the ligand binding to the protein molecule is about 1,000 times slower than that of the covalent bond.

A coarse-grained model of the effective interaction for charged amino acid residues and its application to formation of GCN4-pLI tetramer

ABSTRACT We present a simple coarse-grained model of the effective interaction for charged amino acid residues, such as Glu and Lys, in a water solvent. The free-energy profile as a function of the distance between two charged amino acid side-chain analogues in an explicit water solvent is calculated with all-atom molecular dynamics simulation and thermodynamic integration method. The calculated free-energy profile is applied to the coarse-grained potential of the effective interaction between two amino acid residues. The Langevin dynamics simulations with our coarse-grained potential are performed for association of a small protein complex, GCN4-pLI tetramer. The tetramer conformation reproduced by our coarse-grained model is similar to the X-ray crystallographic structure. We show that the effective interaction between charged amino acid residues stabilises association and orientation of protein complex. We also investigate the association pathways of GCN4-pLI tetramer.

A hybrid-type approach with MD and DFT calculations for evaluation of redox potential of molecules

A simple calculation method to evaluate the redox potential of molecules by using a hybrid-type calculation with molecular dynamics (MD) and density functional theory calculations is presented with discussions of the difference of the redox potential. In our hybrid method, the standard Gibbs free energy of the molecules, acetone and 3-pentanone, in the redox reaction, is estimated from the average of ionisation free energy and the excess chemical potentials of the reduced and oxidised molecules according to the Born–Haber cycle by sampled configurations from the MD simulation. The difference of the redox potentials between the two molecules is in agreement with the experimental data within the standard deviation.

Solvent site-dipole fields around guanine nucleotides in the Hras-GTP complex and in the Hras-GDP complex

Directional correlation of solvent site-dipole field, resulting from orientational ordering of individual water molecules around guanine nucleotides in the Hras-GTP complex and in the Hras-GDP complex, was studied with molecular dynamics simulations of the Hras-GTP and the Hras-GDP complexes in water solution. The coarse-grained time-window-averaged site-dipole fields are different between Hras-GTP and Hras-GDP at some area, although the time-window-averaged site-dipole fields without spatial coarse-graining are not so different. This suggests that, for the orientation of water molecules at special position, the spatial coherence is more important than the temporal coherence for GTP hydrolysis in the Hras-GTP complex.

Molecular Dynamics Study of Hsp90 and ADP: Hydrogen Bond Analysis for ADP Dissociation

The contacts between the N-terminal domain of heat shock protein 90 (N-Hsp90) and ADP involve both direct and water-mediated hydrogen bonds in X-ray crystallographic structure. We perform all-atom molecular dynamics (MD) simulations of N-Hsp90 and ADP to investigate the changes of the hydrogen bond lengths during ADP dissociation. We show the difference between the hydrogen bonds in the crystal structure and MD simulations. Moreover, the N6 group of ADP does not contact with the Cγ group of Asp93, and the hydrogen bonds between Asn51 side chain and ADP are stable in the early step of ADP dissociation.

Analysis of water molecules around GTP in Hras-GTP complex and GDP in Hras-GDP complex by molecular dynamics simulations

We investigate the structures of the Hras-GTP and the Hras-GDP complexes in water solvents in order to understand the mechanism of GTP hydrolysis in the Hras-GTP complex. We performed MD simulations of these complexes in order to study the positions and the orientations of water molecules around the guanosine nucleotides. Using trajectories we calculated the angular distribution of water molecules around the most distant phosphorus from guanosine in our previous work. It was shown that water molecules are distributed evenly in GTP, although unevenly in GDP. This suggests that the trigger of GTP hydrolysis is possibly the attack of water molecule to γ−phosphate from the appropriate direction. In this paper, in order to investigate the role of water molecules in GTP hydrolysis in detail, we calculate the orientation of water molecules. The distribution of the orientation is different between GTP and GDP. In order to investigate the cause of this difference, we examine the hydrogen bonds between water molecules and oxygen atom of the most distant phosphate from guanosine. We find that these hydrogen bonds are formed. We also find that the oxygen atom of hydrogen bond is determined by the position of the water molecule of hydrogen bond.