Journal of Computational Chemistry

Cover image for Vol. 38 Issue 10

Early View (Online Version of Record published before inclusion in an issue)

Edited By: Charles L. Brooks III, Masahiro Ehara, Gernot Frenking, and Peter R. Schreiner

Impact Factor: 3.648

ISI Journal Citation Reports © Ranking: 2015: 41/163 (Chemistry Multidisciplinary)

Online ISSN: 1096-987X

Associated Title(s): International Journal of Quantum Chemistry, Wiley Interdisciplinary Reviews: Computational Molecular Science


  1. 1 - 32
  1. Full Papers

    1. Calculations of solid-state 43Ca NMR parameters: A comparison of periodic and cluster approaches and an evaluation of DFT functionals

      Sean T. Holmes, Shi Bai, Robbie J. Iuliucci, Karl T. Mueller and Cecil Dybowski

      Version of Record online: 24 FEB 2017 | DOI: 10.1002/jcc.24763

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      Calculations of 43Ca magnetic-shielding and quadrupolar-coupling tensors for 10 solids, including inorganic materials and calcium carboxylates, are provided. This study compares the use of calculations using clusters to model a local portion of the lattice with calculations using periodic-boundary conditions. The variation in computed NMR parameters is assessed for Hartree–Fock theory and 17 density functionals based on agreement with experimental values.

    2. Standard grids for high-precision integration of modern density functionals: SG-2 and SG-3

      Saswata Dasgupta and John M. Herbert

      Version of Record online: 24 FEB 2017 | DOI: 10.1002/jcc.24761

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      New quadrature grids have been developed for density functional theory. These grids are designed to provide accurate yet cost-effective evaluation of the current generation of exchange-correlation functionals, which are more demanding in terms of numerical quadrature as compared to the density functionals in widespread use in the 1990s. The relatively sparse “pruned” grids introduced here afford significant speedups with respect to “parent” grids that were selected for accuracy.

    3. How computational methods and relativistic effects influence the study of chemical reactions involving Ru-NO complexes?

      Renato Pereira Orenha, Régis Tadeu Santiago, Roberto Luiz Andrade Haiduke and Sérgio Emanuel Galembeck

      Version of Record online: 16 FEB 2017 | DOI: 10.1002/jcc.24762

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      Nitric oxide shows a relevant role in many biological processes and ruthenium amine complexes can be used to control its availability. Thus, the influence of two different treatments for relativistic effects (ECP or DKH2) is analyzed with respect to geometric parameters and energies of typical chemical reactions involving this class of complexes. Additionally, several electronic structure methods are evaluated comparatively to the reactions energies from CCSD(T).

    4. A multipolar approach to the interatomic covalent interaction energy

      Evelio Francisco, Daniel Menéndez Crespo, Aurora Costales and Ángel Martín Pendás

      Version of Record online: 16 FEB 2017 | DOI: 10.1002/jcc.24758

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      Interatomic or interfragment covalent energies in real space, as measured by the interacting quantum atoms exchange-correlation energies ( inline image) are shown to be well-approximated by a multipolar approximation if terms up to the charge–quadrupole interaction are retained (cdq). The cdq approximation improves considerably the performance of the zeroth-order approximation, in which Vxc is equal to the bond order (delocalization index, δAB) over the interatomic distance.

    5. Gating energetics of a voltage-dependent K+ channel pore domain

      Greg Starek, J. Alfredo Freites, Simon Bernèche and Douglas J. Tobias

      Version of Record online: 16 FEB 2017 | DOI: 10.1002/jcc.24742

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      Free energy calculations suggest multiple energetically favorable conformations of the pore domain of KvAP, a voltage gated potassium ion channel. The energetic landscape is influenced by the hydration of the ion conducting pore. The solvation effects revealed here could bridge seemingly contradictory theoretical and experimental results concerning the mechanism and energetics of gating in voltage-gated potassium ion channels.

    6. Accurate, robust, and reliable calculations of Poisson–Boltzmann binding energies

      Duc D. Nguyen, Bao Wang and Guo-Wei Wei

      Version of Record online: 16 FEB 2017 | DOI: 10.1002/jcc.24757

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      MIBPB ( is a second order accurate Poisson–Boltzmann (PB) online solver. Due to the use of advanced elliptic interface techniques, MIBPB's relative absolute errors in calculating electrostatic solvation free energies and binding free energies are less than 0.3% and 3%, respectively, when the mesh size is refined from 1.1 to 0.2 Å.

  2. Software News and Updates

    1. A new extension of classical molecular dynamics: An electron transfer algorithm

      Anton Raskovalov

      Version of Record online: 16 FEB 2017 | DOI: 10.1002/jcc.24755

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      An extension of molecular dynamics method to include an electron transfer process is suggested. The method samples all electron donor/acceptor pairs where the electron exchange is possible. Then the proposed algorithm chooses an acceptor for an each donor according to the Franck–Condon principle. The final decision of doing electron jump or not is defined via potential energy difference calculation.

  3. Full Papers

    1. Theoretical rationalization for reduced charge recombination in bulky carbazole-based sensitizers in solar cells

      Yaowarat Surakhot, Viktor Laszlo, Chirawat Chitpakdee, Vinich Promarak, Taweesak Sudyoadsuk, Nawee Kungwan, Tim Kowalczyk, Stephan Irle and Siriporn Jungsuttiwong

      Version of Record online: 13 FEB 2017 | DOI: 10.1002/jcc.24751

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      This investigation resolves a discrepancy in the observed photoconversion efficiency (PCE) of two closely related DSCs based on carbazole-containing D–π–A organic sensitizers. Although the two dyes produce similar spectral features, ground- and excited-state density functional theory (DFT) simulations reveal that the dye with the bulkier donor group in CCTA adsorbs more strongly to TiO2, experiences limited π–π aggregation, and is more resistant to loss of excitation energy via charge recombination on the dye. The superior open-circuit voltage and short-circuit current of the bulky-donor dye sensitizer provide theoretical justification of an important design feature for the pursuit of greater photocurrent efficiency in DSCs.


    2. Common folding processes of mini-proteins: Partial formations of secondary structures initiate the immediate protein folding

      Ryuhei Harada, Yu Takano and Yasuteru Shigeta

      Version of Record online: 13 FEB 2017 | DOI: 10.1002/jcc.24748

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      The folding processes of mini-proteins (FSD-EY/FBPWW28 domain) were computationally investigated. Through the analyses of trajectories, these mini-proteins had multiple folding pathways, and their folding processes were initiated by partial formations of secondary structures, that is, FSD-EY (α/β topology) folds by a simple diffusion-collision mechanism, while the folding process of the FBPWW28 domain (all-β topology) requires a modification of the diffusion-collision theory to adequately treat the coil-sheet transition for the β sheet formation.

    3. Insulin mimetic peptide S371 folds into a helical structure

      Hossein Mohammadiarani and Harish Vashisth

      Version of Record online: 12 FEB 2017 | DOI: 10.1002/jcc.24746

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      Insulin mimetic peptides have been recently designed as potent receptor agonists and antagonists. In this article are present structural models of a site 1 mimetic peptide (red transparent cartoons) that is known to compete with a critical hormone-binding helical peptide of the receptor (dark red cartoon) for binding at site 1 (brown cartoon and transparent surface).

    4. Metallic monoboronyl compounds: Prediction of their structure and comparison with the cyanide analogues

      Álvaro Vega-Vega, Carmen Barrientos and Antonio Largo

      Version of Record online: 12 FEB 2017 | DOI: 10.1002/jcc.24752

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      Monoboronyls of representative metals are theoretically studied. Mg (s-block), Al (p-block), and Group 11 metals Cu, Ag, and Au (d-block) have been chosen. The preference for metal-boron or metal-oxygen bonding is discussed and relevant spectroscopic parameters predicted. A comparison with the analogue metal-cyanide compounds is carried out emphasizing the similarities and differences between the isoelectronic boronyl and cyanide ligands.

    5. Systematic study of the effect of HSE functional internal parameters on the electronic structure and band gap of a representative set of metal oxides

      Francesc Viñes, Oriol Lamiel-García, Kyoung Chul Ko, Jin Yong Lee and Francesc Illas

      Version of Record online: 4 FEB 2017 | DOI: 10.1002/jcc.24744

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      The effect of the amount of Fock exchange and of the screening parameter defining the range separated HSE type hybrid functional is systematically studied for a series of seven metal oxides to define the combination of two parameters reproducing the band gap.

    6. Heterogeneous dielectric generalized Born model with a van der Waals term provides improved association energetics of membrane-embedded transmembrane helices

      Bercem Dutagaci, Maryam Sayadi and Michael Feig

      Version of Record online: 4 FEB 2017 | DOI: 10.1002/jcc.24691

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      The implicit membrane model of Heterogeneous Dielectric Generalized Born with a van der Waals term is introduced with an additional dispersion term. The new modification of the model provides a more accurate description of the total nonpolar free energy, which consists of repulsive and attractive components. This novel description of the implicit model improved the agreement of the free energy of association of transmembrane helix dimers in significant amount.

    7. Revealing the physical nature and the strength of charge-inverted hydrogen bonds by SAPT(DFT), MP2, SCS-MP2, MP2C, and CCSD(T) methods

      Sirous Yourdkhani and Mirosław Jabłoński

      Version of Record online: 31 JAN 2017 | DOI: 10.1002/jcc.24739

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      The physical nature of charge-inverted hydrogen bonds in H3XH inline imageYH3 (X = Si, Ge; Y = Al, Ga) dimer systems is studied by means of SAPT(DFT)-based decomposition of interaction energies and supermolecular interaction energies based on MP2, SCS-MP2, MP2C, and CCSD(T) methods. Inductive nature of charge-inverted hydrogen bonds in investigated systems is revealed, although dispersion term is also important.

    8. Prediction of consensus binding mode geometries for related chemical series of positive allosteric modulators of adenosine and muscarinic acetylcholine receptors

      Leon A. Sakkal, Kyle Z. Rajkowski and Roger S. Armen

      Version of Record online: 28 JAN 2017 | DOI: 10.1002/jcc.24728

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      A3R partial-agonist inosine, in the presence of positive allosteric modulator LUF6000, exhibits three-fold increased activity. Docking studies predict LUF6000 binding in a “capping” interaction through a hydrogen bond with the carbonyl group of inosine. The interaction between the molecular structures of LUF6000 and inosine may explain the increase in activity. This interaction is inosine-specific, and is not seen with radioligand MRS-542, which lacks a carbonyl group.

    9. Membrane insertion of fusion peptides from Ebola and Marburg viruses studied by replica-exchange molecular dynamics simulations

      Mark A. Olson, Michael S. Lee and In-Chul Yeh

      Version of Record online: 28 JAN 2017 | DOI: 10.1002/jcc.24717

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      Potential of mean force as a function of the center-of-mass Z-axis and a conformational snapshot extracted from a replica-exchange molecular dynamics simulation of peptide insertion into a membrane bilayer for a 16-residue Ebola virus fusion peptide. The membrane-aqueous bilayer is described by a generalized Born continuum model with a smoothed switching function. A comparative analysis is presented of the mutant W8A and a fusion peptide from the Marburg virus.

    10. Evaluation of the hybrid resolution PACE model for the study of folding, insertion, and pore formation of membrane associated peptides

      Michael D. Ward, Shivangi Nangia and Eric R. May

      Version of Record online: 19 JAN 2017 | DOI: 10.1002/jcc.24694

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      The hybrid resolution PACE model has been applied to several well studied peptidemembrane systems. The simulations show that PACE provides a reasonably accurate model to study simple peptide topologies, such as single pass transmembrane helices. However, we find PACE does not maintain the native helical hairpin structure of the influenza hemagglutinin fusion peptide, which may be caused by an unfavorable electrostatic interaction in the model.

    11. Rigidity and flexibility in the tetrasaccharide linker of proteoglycans from atomic-resolution molecular simulation

      Cathy Ng, Padmavathy Nandha Premnath and Olgun Guvench

      Version of Record online: 19 JAN 2017 | DOI: 10.1002/jcc.24738

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      All-atom explicit-solvent molecular dynamics simulations show strong preferences for single conformations about glycosidic linkages between disaccharides in the proteoglycan linker tetrasaccharide. In contrast, the linkage between the first monosaccharide and the protein core, Xylβ1-O-Ser, shows significant flexibility with multiple likely conformations. The complete conjugate can be thought of as a mathematical vector, with the tetrasaccharide determining the length and the Xyl-Ser linkage the direction.

    12. Extreme biophysics: Enzymes under pressure

      Qi Huang, Jocelyn M. Rodgers, Russell J. Hemley and Toshiko Ichiye

      Version of Record online: 19 JAN 2017 | DOI: 10.1002/jcc.24737

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      Determining adaptations of enzymes for extreme pressure and temperature is important for understanding structure-function relationships in enzymes and may help in defining the “limits of life.” Atomistic simulations of dihydrofolate reductase from a mesophile and a “piezophile” identify collective motions as responsible for the flexibility necessary for “corresponding states” enzyme activity. In addition, the adaptions for low temperature and high pressure environment of deep-sea microbes are identified as greater flexibility and lower density.

    13. You have full text access to this OnlineOpen article
      The free energy of locking a ring: Changing a deoxyribonucleoside to a locked nucleic acid

      You Xu, Alessandra Villa and Lennart Nilsson

      Version of Record online: 19 JAN 2017 | DOI: 10.1002/jcc.24692

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      Locked nucleic acids (LNA) are widely used in gene therapeutic field, for its well-known high stabilization on DNA helical structures. While it is the interesting to calculate what the difference of its free energy contributions are from DNA, the technical difficulty of transforming a bridged-ring remains. This study describes the protocols of calculating free energy difference between LNA and DNA using MD simulations and Bennett Acceptance Ratio.

    14. In situ data analytics and indexing of protein trajectories

      Travis Johnston, Boyu Zhang, Adam Liwo, Silvia Crivelli and Michela Taufer

      Version of Record online: 17 JAN 2017 | DOI: 10.1002/jcc.24729

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      As computing moves toward exascale, I/O bandwidth limitations and power concerns will require a fundamental change in the way data is analyzed and stored. We present a novel method of analyzing and indexing protein trajectory data in situ. The analysis computes metadata for conformations as they are generated during a simulation. The indexed trajectory can then be quickly examined and in depth analysis can be performed on the most relevant segments of a trajectory.

    15. Computing conformational free energy differences in explicit solvent: An efficient thermodynamic cycle using an auxiliary potential and a free energy functional constructed from the end points

      Robert C. Harris, Nanjie Deng, Ronald M. Levy, Ryosuke Ishizuka and Nobuyuki Matubayasi

      Version of Record online: 23 DEC 2016 | DOI: 10.1002/jcc.24668

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      The free energy differences associated with conformational changes are difficult to compute in explicit solvent. Instead, these free energy differences can be computed on an auxiliary free energy surface and the desired free energy difference obtained by adding the free energies of transferring the end states from the auxiliary surface to the target surface. Here, we show that computing these transfer free energies with the energy representation method substantially reduces the cost of these calculations.

    16. You have full text access to this OnlineOpen article
      Computing infrared spectra of proteins using the exciton model

      Fouad S. Husseini, David Robinson, Neil T. Hunt, Anthony W. Parker and Jonathan D. Hirst

      Version of Record online: 21 NOV 2016 | DOI: 10.1002/jcc.24674

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      The ability to compute from first principles the infrared spectrum of a protein would provide a useful connection to atomistic models of structure and dynamics. This linkage is shown in the figure for the β-sheet protein concanavalin A (one of several proteins we study) with amide I spectra from a molecular dynamics simulation, for the snapshots with spectra most similar (dashed blue), and least similar (dotted red) to the computed average spectra (solid black).

    17. On the importance of composite protein multiple ligand interactions in protein pockets

      Sam Tonddast-Navaei, Bharath Srinivasan and Jeffrey Skolnick

      Version of Record online: 16 NOV 2016 | DOI: 10.1002/jcc.24523

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      The canonical view of protein–ligand interaction is focused on one ligand per pocket at a time. Here, we present the concept of a COmposite Protein LIGands (COLIG), as multiple interacting ligands in the same pocket. Our analysis shows that majority of proteins can bind COLIGs and most ligands can form COLIGs. Finally, we find that ligands tend to bind in the deepest locations of the largest pocket of a protein.

  4. Reviews

    1. CHARMM-GUI 10 years for biomolecular modeling and simulation

      Sunhwan Jo, Xi Cheng, Jumin Lee, Seonghoon Kim, Sang-Jun Park, Dhilon S. Patel, Andrew H. Beaven, Kyu Il Lee, Huan Rui, Soohyung Park, Hui Sun Lee, Benoît Roux, Alexander D. MacKerell Jr, Jeffrey B. Klauda, Yifei Qi and Wonpil Im

      Version of Record online: 14 NOV 2016 | DOI: 10.1002/jcc.24660

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      CHARMM-GUI,, is a web-based graphical user interface that can be used to prepare complex biomolecular simulation systems and input files (for CHARMM, NAMD, GROMACS, AMBER, GENESIS, LAMMPS, Desmond, OpenMM, and CHARMM/OpenMM) to facilitate the usage of common and advanced simulation techniques.

  5. Full Papers

    1. You have full text access to this OnlineOpen article
      A QM/MM study of the nature of the entatic state in plastocyanin

      Catherine A. Hurd, Nicholas A. Besley and David Robinson

      Version of Record online: 14 NOV 2016 | DOI: 10.1002/jcc.24666

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      The nature of the entatic state in plastocyanin is studied through density functional theory-based QM/MM calculations. The strain energy is computed to be 12.8 kcal/mol and 14.5 kcal/mol for the oxidized and reduced forms of the protein. Accurate calculation of the reorganization energy for the electron transfer protein requires conformation averaging and large region around the active site to be treated at the quantum mechanical level.


    1. Molecular simulations to delineate functional conformational transitions in the HCV polymerase

      Ester Sesmero, Jodian A. Brown and Ian F. Thorpe

      Version of Record online: 12 NOV 2016 | DOI: 10.1002/jcc.24662

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      The Hepatitis C virus polymerase adopts distinct conformations in replicating the viral RNA genome. Molecular dynamics simulations reveal the physical nature of these states in previously unavailable detail, as well as the molecular interactions that allow the enzyme to transition between them. These studies provide invaluable information regarding the fundamental processes that govern RNA replication performed by the polymerase and contribute to improving our comprehension of molecular mechanisms by which therapeutics may target this enzyme.

  7. Full Papers

    1. PB-AM: An open-source, fully analytical linear poisson-boltzmann solver

      Lisa E. Felberg, David H. Brookes, Eng-Hui Yap, Elizabeth Jurrus, Nathan A. Baker and Teresa Head-Gordon

      Version of Record online: 2 NOV 2016 | DOI: 10.1002/jcc.24528

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      Visualization of electrostatic potential isosurface of charge-driven interaction between barnase (bottom left) and barstar (upper right) molecules, generated from the Poisson-Boltzmann Analytical Method (PB-AM) software. The PB-AM software is a user-friendly, fully analytical solver for the Poisson-Boltzmann equation.

    2. Estimation of relative free energies of binding using pre-computed ensembles based on the single-step free energy perturbation and the site-identification by Ligand competitive saturation approaches

      E. Prabhu Raman, Sirish Kaushik Lakkaraju, Rajiah Aldrin Denny and Alexander D. MacKerell Jr

      Version of Record online: 26 OCT 2016 | DOI: 10.1002/jcc.24522

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      Accurate and rapid prediction of ligand potencies by the pre-computed ensembles based methods, Single Step Free Energy Perturbation (SSFEP) and Site Identification by Ligand Competitive Saturation (SILCS), is evaluated for Ack1 and p38 Map Kinase targets. Both SILCS and SSFEP are competitive with or better than the FEP results for the studied systems while being 1000+ fold times faster. Potential application of these methods in the context of screening large numbers of transformations is also illustrated.

  8. Full Paper

    1. Optimal allosteric stabilization sites using contact stabilization analysis

      Alex Dickson, Christopher T. Bailey and John Karanicolas

      Version of Record online: 24 OCT 2016 | DOI: 10.1002/jcc.24517

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      Proteins are prone to unfold and aggregate, especially when mutated or under stress. Stabilizing a proteins' functional state, either using engineered disulfide bonds or designed small-molecule stabilizers, is an important goal, but first we must determine an optimal stabilization site to impact activity. We use simulation to measure the stabilization capacity of every contact in the β-glucuronidase enzyme, and show that the stabilization capacity of a contact is only loosely related to its proximity from the active site.

  9. Full Papers

    1. Exploring the structure and stability of cholesterol dimer formation in multicomponent lipid bilayers

      Asanga Bandara, Afra Panahi, George A. Pantelopulos and John E. Straub

      Version of Record online: 20 OCT 2016 | DOI: 10.1002/jcc.24516

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      The existence of cholesterol dimers has long been proposed to be important to the function of cholesterol in facilitating membrane domain formation and lipid–protein interaction. Molecular dynamics simulation is used to characterize the structure and stability of the cholesterol dimer, as well as its dependence on membrane lipid composition. The results support the existence of a variety of cholesterol dimer structures, the nature of which may be critical to our understanding of cholesterol's function.

    2. Multiple program/multiple data molecular dynamics method with multiple time step integrator for large biological systems

      Jaewoon Jung and Yuji Sugita

      Version of Record online: 6 OCT 2016 | DOI: 10.1002/jcc.24511

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      We propose a novel parallelization scheme for large-scale MD simulations on massively parallel supercomputer with only CPUs. In the scheme, we introduce multiple program/multiple data (MPMD) approach based on midpoint cell method (Jung et al., J. Comput. Chem. 2014, 35, 1064) combined with volumetric decomposition fast Fourier transform (J. Jung et al., Comput. Phys. Commun. 2016, 200, 57). The new approach increases the parallel performance for large number of processors by assigning the same domain decomposition between real- and reciprocal-spaces. Moreover, we optimize the speed by properly making use of multiple time step integrator with MPMD. We obtain very good performance of our method on K computer.


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