Performance information

• Explicit description of viral capsid subunit shapes by unfolding dihedrons　　　　　　　　　　　　　　　
  Ryuya Toyooka; Seri Nishimoto; Tomoya Tendo; Takashi Horiyama; Tomohiro Tachi; Yasuhiro Matsunaga
  Communications Biology, Nov. 2024
  Scientific journal
  DOI：https://doi.org/10.1038/s42003-024-07218-x
  DOI ID：10.1038/s42003-024-07218-x, ORCID：171737880
• GENESIS 2.1: High-Performance Molecular Dynamics Software for Enhanced Sampling and Free-Energy Calculations for Atomistic, Coarse-Grained, and Quantum Mechanics/Molecular Mechanics Models　　　　　　　　　　　　　　　
  Jaewoon Jung; Kiyoshi Yagi; Cheng Tan; Hiraku Oshima; Takaharu Mori; Isseki Yu; Yasuhiro Matsunaga; Chigusa Kobayashi; Shingo Ito; Diego Ugarte La Torre; Yuji Sugita
  The Journal of Physical Chemistry B, Jun. 2024
  Scientific journal
  DOI：https://doi.org/10.1021/acs.jpcb.4c02096
  DOI ID：10.1021/acs.jpcb.4c02096, ORCID：161636064
• Representation of Protein Dynamics Disentangled by Time-Structure-Based Prior
  Tsuyoshi Ishizone; Yasuhiro Matsunaga; Sotaro Fuchigami; Kazuyuki Nakamura
  Journal of Chemical Theory and Computation, Volume：20, Number：1, First page：436, Last page：450, Dec. 2023
  American Chemical Society (ACS), Scientific journal
  DOI：https://doi.org/10.1021/acs.jctc.3c01025
  DOI ID：10.1021/acs.jctc.3c01025, ISSN：1549-9618, eISSN：1549-9626
• End-to-end differentiable blind tip reconstruction for noisy atomic force microscopy images.　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga; Sotaro Fuchigami; Tomonori Ogane; Shoji Takada
  Scientific reports, Volume：13, Number：1, First page：129, Last page：129, Jan. 2023, ［International magazine］
  Observing the structural dynamics of biomolecules is vital to deepening our understanding of biomolecular functions. High-speed (HS) atomic force microscopy (AFM) is a powerful method to measure biomolecular behavior at near physiological conditions. In the AFM, measured image profiles on a molecular surface are distorted by the tip shape through the interactions between the tip and molecule. Once the tip shape is known, AFM images can be approximately deconvolved to reconstruct the surface geometry of the sample molecule. Thus, knowing the correct tip shape is an important issue in the AFM image analysis. The blind tip reconstruction (BTR) method developed by Villarrubia (J Res Natl Inst Stand Technol 102:425, 1997) is an algorithm that estimates tip shape only from AFM images using mathematical morphology operators. While the BTR works perfectly for noise-free AFM images, the algorithm is susceptible to noise. To overcome this issue, we here propose an alternative BTR method, called end-to-end differentiable BTR, based on a modern machine learning approach. In the method, we introduce a loss function including a regularization term to prevent overfitting to noise, and the tip shape is optimized with automatic differentiation and backpropagations developed in deep learning frameworks. Using noisy pseudo-AFM images of myosin V motor domain as test cases, we show that our end-to-end differentiable BTR is robust against noise in AFM images. The method can also detect a double-tip shape and deconvolve doubled molecular images. Finally, application to real HS-AFM data of myosin V walking on an actin filament shows that the method can reconstruct the accurate surface geometry of actomyosin consistent with the structural model. Our method serves as a general post-processing for reconstructing hidden molecular surfaces from any AFM images. Codes are available at https://github.com/matsunagalab/differentiable_BTR .
  Springer Science and Business Media {LLC}, English, Scientific journal
  DOI：https://doi.org/10.1038/s41598-022-27057-2
  DOI ID：10.1038/s41598-022-27057-2, ISSN：2045-2322, ORCID：125877151, PubMed ID：36599879
• Development of hidden Markov modeling method for molecular orientations and structure estimation from high-speed atomic force microscopy time-series images.　　　　　　　　　　　　　　　
  Tomonori Ogane; Daisuke Noshiro; Toshio Ando; Atsuko Yamashita; Yuji Sugita; Yasuhiro Matsunaga
  PLoS computational biology, Volume：18, Number：12, First page：e1010384, Dec. 2022, ［International magazine］
  High-speed atomic force microscopy (HS-AFM) is a powerful technique for capturing the time-resolved behavior of biomolecules. However, structural information in HS-AFM images is limited to the surface geometry of a sample molecule. Inferring latent three-dimensional structures from the surface geometry is thus important for getting more insights into conformational dynamics of a target biomolecule. Existing methods for estimating the structures are based on the rigid-body fitting of candidate structures to each frame of HS-AFM images. Here, we extend the existing frame-by-frame rigid-body fitting analysis to multiple frames to exploit orientational correlations of a sample molecule between H frames in HS-AFM data due to the interaction with the stage. In the method, we treat HS-AFM data as time-series data, and they are analyzed with the hidden Markov modeling. Using simulated HS-AFM images of the taste receptor type 1 as a test case, the proposed method shows a more robust estimation of molecular orientations than the frame-by-frame analysis. The method is applicable in integrative modeling of conformational dynamics using HS-AFM data.
  English, Scientific journal
  DOI：https://doi.org/10.1371/journal.pcbi.1010384
  DOI ID：10.1371/journal.pcbi.1010384, PubMed ID：36580448, PubMed Central ID：PMC9833559
• Use of multistate Bennett acceptance ratio method for free-energy calculations from enhanced sampling and free-energy perturbation　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga; Motoshi Kamiya; Hiraku Oshima; Jaewoon Jung; Shingo Ito; Yuji Sugita
  Biophysical Reviews, Dec. 2022
  AbstractMultistate Bennett acceptance ratio (MBAR) works as a method to analyze molecular dynamics (MD) simulation data after the simulations have been finished. It is widely used to estimate free-energy changes between different states and averaged properties at the states of interest. MBAR allows us to treat a wide range of states from those at different temperature/pressure to those with different model parameters. Due to the broad applicability, the MBAR equations are rather difficult to apply for free-energy calculations using different types of MD simulations including enhanced conformational sampling methods and free-energy perturbation. In this review, we first summarize the basic theory of the MBAR equations and categorize the representative usages into the following four: (i) perturbation, (ii) scaling, (iii) accumulation, and (iv) full potential energy. For each, we explain how to prepare input data using MD simulation trajectories for solving the MBAR equations. MBAR is also useful to estimate reliable free-energy differences using MD trajectories based on a semi-empirical quantum mechanics/molecular mechanics (QM/MM) model and ab initio QM/MM energy calculations on the MD snapshots. We also explain how to use the MBAR software in the GENESIS package, which we call mbar_analysis, for the four representative cases. The proposed estimations of free-energy changes and thermodynamic averages are effective and useful for various biomolecular systems.
  Springer Science and Business Media {LLC}, English, Scientific journal
  DOI：https://doi.org/10.1007/s12551-022-01030-9
  DOI ID：10.1007/s12551-022-01030-9, ISSN：1867-2450, ORCID：125877041
• Construction of a Humanized Artificial VHH Library Reproducing Structural Features of Camelid VHHs for Therapeutics
  Taihei Murakami; Shigefumi Kumachi; Yasuhiro Matsunaga; Miwa Sato; Kanako Wakabayashi-Nakao; Hidekazu Masaki; Ryo Yonehara; Maiko Motohashi; Naoto Nemoto; MASAYUKI TSUCHIYA
  Antibodies, Volume：11, Number：1, First page：10, Last page：10, Jan. 2022
  A variable domain of heavy chain antibody (VHH) has different binding properties than conventional antibodies. Conventional antibodies prefer binding to the convex portion of the antigen, whereas VHHs prefer epitopes, such as crevices and clefts on the antigen. Therefore, developing candidates with the binding characteristics of camelid VHHs is important. Thus, To this end, a synthetic VHH library that reproduces the structural properties of camelid VHHs was constructed. First, the characteristics of VHHs were classified according to the paratope formation based on crystal structure analyses of the complex structures of VHHs and antigens. Then, we classified 330 complementarity-determining region 3 (CDR3) structures of VHHs from the Protein Data Bank (PDB) into three loop structures: Upright, Half-Roll, and Roll. Moreover, these structures depended on the number of amino acid residues within CDR3. Furthermore, in the Upright loops, several amino acid residues in the FR2 are involved in the paratope formation, along with CDR3, suggesting that the FR2 design in the synthetic library is important. A humanized synthetic VHH library, comprising two sub-libraries, Upright and Roll, was constructed and named PharmaLogical. A validation study confirmed that our PharmaLogical library reproduces VHHs with the characteristics of the paratope formation of the camelid VHHs, and shows good performance in VHH screening.
  MDPI AG, Scientific journal
  DOI：https://doi.org/10.3390/antib11010010
  DOI ID：10.3390/antib11010010, eISSN：2073-4468, ORCID：107604526
• Enhanced Conformational Sampling of Nanobody CDR H3 Loop by Generalized Replica-Exchange with Solute Tempering
  Ren Higashida; Yasuhiro Matsunaga
  Life, Volume：11, Number：12, First page：1428, Last page：1428, Dec. 2021
  The variable domains of heavy-chain antibodies, known as nanobodies, are potential substitutes for IgG antibodies. They have similar affinities to antigens as antibodies, but are more heat resistant. Their small size allows us to exploit computational approaches for structural modeling or design. Here, we investigate the applicability of an enhanced sampling method, a generalized replica-exchange with solute tempering (gREST) for sampling CDR-H3 loop structures of nanobodies. In the conventional replica-exchange methods, temperatures of only a whole system or scaling parameters of a solute molecule are selected for temperature or parameter exchange. In gREST, we can flexibly select a part of a solute molecule and a part of the potential energy terms as a parameter exchange region. We selected the CDR-H3 loop and investigated which potential energy term should be selected for the efficient sampling of the loop structures. We found that the gREST with dihedral terms can explore a global conformational space, but the relaxation to the global equilibrium is slow. On the other hand, gREST with all the potential energy terms can sample the equilibrium distribution, but the structural exploration is slower than with dihedral terms. The lessons learned from this study can be applied to future studies of loop modeling.
  MDPI AG, Scientific journal
  DOI：https://doi.org/10.3390/life11121428
  DOI ID：10.3390/life11121428, eISSN：2075-1729, ORCID：105204808
• Structural and energetic analysis of metastable intermediate states in the E1P–E2P transition of Ca2+-ATPase
  Chigusa Kobayashi; Yasuhiro Matsunaga; Jaewoon Jung; Yuji Sugita
  Proceedings of the National Academy of Sciences, Volume：118, Number：40, First page：e2105507118, Last page：e2105507118, Oct. 2021
  Sarcoplasmic reticulum (SR) Ca²⁺-ATPase transports two Ca²⁺ ions from the cytoplasm to the SR lumen against a large concentration gradient. X-ray crystallography has revealed the atomic structures of the protein before and after the dissociation of Ca²⁺, while biochemical studies have suggested the existence of intermediate states in the transition between E1P⋅ADP⋅2Ca²⁺ and E2P. Here, we explore the pathway and free energy profile of the transition using atomistic molecular dynamics simulations with the mean-force string method and umbrella sampling. The simulations suggest that a series of structural changes accompany the ordered dissociation of ADP, the A-domain rotation, and the rearrangement of the transmembrane (TM) helices. The luminal gate then opens to release Ca²⁺ ions toward the SR lumen. Intermediate structures on the pathway are stabilized by transient sidechain interactions between the A- and P-domains. Lipid molecules between TM helices play a key role in the stabilization. Free energy profiles of the transition assuming different protonation states suggest rapid exchanges between Ca²⁺ ions and protons when the Ca²⁺ ions are released toward the SR lumen.
  Proceedings of the National Academy of Sciences, Scientific journal
  DOI：https://doi.org/10.1073/pnas.2105507118
  DOI ID：10.1073/pnas.2105507118, ISSN：0027-8424, eISSN：1091-6490
• Coarse-Grained Modeling of Multiple Pathways in Conformational Transitions of Multi-Domain Proteins　　　　　　　　　　　　　　　
  Ai Shinobu; Chigusa Kobayashi; Yasuhiro Matsunaga; Yuji Sugita
  Journal of Chemical Information and Modeling, Volume：61, Number：5, First page：2427, Last page：2443, May 2021
  American Chemical Society (ACS), Scientific journal
  DOI：https://doi.org/10.1021/acs.jcim.1c00286
  DOI ID：10.1021/acs.jcim.1c00286, ISSN：1549-9596, eISSN：1549-960X, DBLP ID：journals/jcisd/ShinobuKMS21
• Rigid-body fitting to atomic force microscopy images for inferring probe shape and biomolecular structure.　　　　　　　　　　　　　　　
  Toru Niina; Yasuhiro Matsunaga; Shoji Takada
  PLoS Computational Biology, Volume：17, Number：7, 2021
  Scientific journal
  DOI：https://doi.org/10.1371/journal.pcbi.1009215
  DOI ID：10.1371/journal.pcbi.1009215, DBLP ID：journals/ploscb/NiinaMT21
• Weighted ensemble simulations for conformational changes of proteins
  Hiroshi Fujisaki; Yasuhiro Matsunaga; Kei Moritsugu
  INTERNATIONAL CONFERENCE OF COMPUTATIONAL METHODS IN SCIENCES AND ENGINEERING ICCMSE 2020, 2021
  AIP Publishing, International conference proceedings
  DOI：https://doi.org/10.1063/5.0047730
  DOI ID：10.1063/5.0047730
• Use of single-molecule time-series data for refining conformational dynamics in molecular simulations　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga; Yuji Sugita
  Current Opinion in Structural Biology, Volume：61, First page：153, Last page：159, Apr. 2020
  Elsevier {BV}, English, Scientific journal
  DOI：https://doi.org/10.1016/j.sbi.2019.12.022
  DOI ID：10.1016/j.sbi.2019.12.022, ISSN：0959-440X, ORCID：125877227
• Drug Transport Mechanism of Multidrug Transporter AcrB Studied by Molecular Dynamics Simulations
  Yasuhiro MATSUNAGA
  Seibutsu Butsuri, Volume：59, Number：2, First page：084, Last page：087, 2019
  Biophysical Society of Japan, Scientific journal
  DOI：https://doi.org/10.2142/biophys.59.084
  DOI ID：10.2142/biophys.59.084, ISSN：0582-4052, eISSN：1347-4219
• Building a macro-mixing dual‑basin Gō model using the Multistate Bennett Acceptance Ratio
  Ai Shinobu; Chigusa Kobayashi; Yasuhiro Matsunaga; Yuji Sugita
  Biophysics and Physicobiology, Volume：16, Number：0, First page：310, Last page：321, 2019
  Biophysical Society of Japan, Scientific journal
  DOI：https://doi.org/10.2142/biophysico.16.0_310
  DOI ID：10.2142/biophysico.16.0_310, eISSN：2189-4779
• Exploring Configuration Space and Path Space of Biomolecules Using Enhanced Sampling Techniques—Searching for Mechanism and Kinetics of Biomolecular Functions　　　　　　　　　　　　　　　
  H. Fujisaki; K. Moritsugu; Y. Matsunaga
  International Journal of Molecular Sciences, Volume：19, Number：10, First page：3177 (19 pages), Oct. 2018, [Reviewed], [Invited], ［International magazine］
  To understand functions of biomolecules such as proteins, not only structures but their conformational change and kinetics need to be characterized, but its atomistic details are hard to obtain both experimentally and computationally. Here, we review our recent computational studies using novel enhanced sampling techniques for conformational sampling of biomolecules and calculations of their kinetics. For efficiently characterizing the free energy landscape of a biomolecule, we introduce the multiscale enhanced sampling method, which uses a combined system of atomistic and coarse-grained models. Based on the idea of Hamiltonian replica exchange, we can recover the statistical properties of the atomistic model without any biases. We next introduce the string method as a path search method to calculate the minimum free energy pathways along a multidimensional curve in high dimensional space. Finally we introduce novel methods to calculate kinetics of biomolecules based on the ideas of path sampling: one is the Onsager⁻Machlup action method, and the other is the weighted ensemble method. Some applications of the above methods to biomolecular systems are also discussed and illustrated.
  English, Scientific journal
  DOI：https://doi.org/10.3390/ijms19103177
  DOI ID：10.3390/ijms19103177, PubMed ID：30326661, PubMed Central ID：PMC6213965
• Linking time-series of single-molecule experiments with molecular dynamics simulations by machine learning　　　　　　　　　　　　　　　
  Matsunaga, Yasuhiro; Sugita, Yuji
  Elife, Volume：7, First page：e32668 (19 pages), May 2018, [Reviewed]
  English, Scientific journal
  DOI：https://doi.org/10.7554/e.Life.32668
  DOI ID：10.7554/e.Life.32668, ORCID：51182310, Web of Science ID：WOS:000431288400001
• Refining Markov state models for conformational dynamics using ensemble-averaged data and time-series trajectories　　　　　　　　　　　　　　　
  Matsunaga, Y.; Sugita, Y.
  Journal of Chemical Physics, Volume：148, Number：24, First page：241731 (7 pages), Apr. 2018, [Reviewed], [Invited]
  English, Scientific journal
  DOI：https://doi.org/10.1063/1.5019750
  DOI ID：10.1063/1.5019750, ORCID：51182312, Web of Science ID：WOS:000437190300034
• Energetics and conformational pathways of functional rotation in the multidrug transporter AcrB　　　　　　　　　　　　　　　
  Y. Matsunaga; T. Yamane; T. Terada; K. Moritsugu; H. Fujisaki; S. Murakami; M. Ikeguchi; A. Kidera
  eLife, Volume：7, First page：e31715 (19 pages), Mar. 2018, [Reviewed]
  The multidrug transporter AcrB transports a broad range of drugs out of the cell by means of the proton-motive force. The asymmetric crystal structure of trimeric AcrB suggests a functionally rotating mechanism for drug transport. Despite various supportive forms of evidence from biochemical and simulation studies for this mechanism, the link between the functional rotation and proton translocation across the membrane remains elusive. Here, calculating the minimum free energy pathway of the functional rotation for the complete AcrB trimer, we describe the structural and energetic basis behind the coupling between the functional rotation and the proton translocation at atomic resolution. Free energy calculations show that protonation of Asp408 in the transmembrane portion of the drug-bound protomer drives the functional rotation. The conformational pathway identifies vertical shear motions among several transmembrane helices, which regulate alternate access of water in the transmembrane as well as peristaltic motions that pump drugs in the periplasm.
  ELIFE SCIENCES PUBLICATIONS LTD, English, Scientific journal
  DOI：https://doi.org/10.7554/eLife.31715
  DOI ID：10.7554/eLife.31715, ISSN：2050-084X, Web of Science ID：WOS:000426766300001
• Molecular Dynamics Simulations for Conformational Changes on a Reaction Step of SR-Ca2+ -ATPase　　　　　　　　　　　　　　　
  Kobayashi, Chigusa; Matsunaga, Yasuhiro; Jung, Jaewoon; Sugita, Yuji
  Biophysical Journal, Volume：114, Number：3, 2018
  Scientific journal
  ORCID：51182311, Web of Science ID：WOS:000430450000202
• Combining Weighted Ensemble Method and Lyapunov Weighted Dynamics: Application to Proteins　　　　　　　　　　　　　　　
  Fujisaki, Hiroshi; Moritsugu, Kei; Matsunaga, Yasuhiro; Suetani, Hiromichi
  Biophysical Journal, Volume：114, Number：3, 2018
  Scientific journal
  ORCID：51182307, Web of Science ID：WOS:000430563300377
• GENESIS 1.1: A hybrid-parallel molecular dynamics simulator with enhanced sampling algorithms on multiple computational platforms　　　　　　　　　　　　　　　
  C. Kobayashi; J. Jung; Y. Matsunaga; T. Mori; T. Ando; K. Tamura; M. Kamiya; Y. Sugita
  Journal of Computational Chemistry, Volume：38, Number：25, First page：2193, Last page：2206, Jul. 2017, [Reviewed]
  English, Scientific journal
  DOI：https://doi.org/10.1002/jcc.24874
  DOI ID：10.1002/jcc.24874, DBLP ID：journals/jcc/KobayashiJMMATK17
• Dimensionality of Collective Variables for Describing Conformational Changes of a Multi-Domain Protein　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga; Yasuaki Komuro; Chigusa Kobayashi; Jaewoon Jung; Takaharu Mori; Yuji Sugita
  JOURNAL OF PHYSICAL CHEMISTRY LETTERS, Volume：7, Number：8, First page：1446, Last page：1451, Apr. 2016, [Reviewed]
  Collective variables (CVs) are often used in molecular dynamics simulations based on enhanced sampling algorithms to investigate large conformational changes of a protein. The choice of CVs in these simulations is essential because it affects simulation results and impacts the free-energy profile, the minimum free-energy pathway (MFEP), and the transition-state structure. Here we examine how many CVs are required to capture the correct transition-state structure during the open-to-close motion of adenylate kinase using a coarse-grained model in the mean forces string method to search the MFEP. Various numbers of large amplitude principal components are tested as CVs in the simulations. The incorporation of local coordinates into CVs, which is possible in higher dimensional CV spaces, is important for capturing a Hummer is sensitive to the choice of CVs, showing sharp peaks reliable MFEP. The Bayesian measure proposed by Best and when the transition-state structure is captured. We thus evaluate the required number of CVs needed in enhanced sampling simulations for describing protein conformational changes.
  AMER CHEMICAL SOC, English, Scientific journal
  DOI：https://doi.org/10.1021/acs.jpclett.6b00317
  DOI ID：10.1021/acs.jpclett.6b00317, ISSN：1948-7185, Web of Science ID：WOS:000374810800007
• Domain Motion Enhanced (DoME) Model for Efficient Conformational Sampling of Multidomain Proteins　　　　　　　　　　　　　　　
  Chigusa Kobayashi; Yasuhiro Matsunaga; Ryotaro Koike; Motonori Ota; Yuji Sugita
  JOURNAL OF PHYSICAL CHEMISTRY B, Volume：119, Number：46, First page：14584, Last page：14593, Nov. 2015, [Reviewed]
  Large conformational changes of multidomain proteins are difficult to simulate using all-atom molecular dynamics (MD) due to the slow time scale. We show that a simple modification of the structure-based coarse-grained (CG) model enables a stable and efficient MD simulation of those proteins. Motion Tree, a tree diagram that describes conformational changes between two structures in a protein, provides information on rigid structural units (domains) and the magnitudes of domain motions. In our new CG model, which we call the DoME (domain motion enhanced) model, interdomain interactions are defined as being inversely proportional to the magnitude of the domain motions in the diagram, whereas intradomain interactions are kept constant. We applied the DoME model in combination with the Go model to simulations of adenylate kinase (AdK). The results of the DoME-Go simulation are consistent with an all-atom MD simulation for 10 mu s as well as known experimental data. Unlike the conventional Go model, the DoME-Go model yields stable simulation trajectories against temperature changes and conformational transitions are easily sampled despite domain rigidity. Evidently, identification of domains and their interfaces is useful approach for CG modeling of multidomain proteins.
  AMER CHEMICAL SOC, English, Scientific journal
  DOI：https://doi.org/10.1021/acs.jpcb.5b07668
  DOI ID：10.1021/acs.jpcb.5b07668, ISSN：1520-6106, Web of Science ID：WOS:000365463200003
• GENESIS: a hybrid-parallel and multi-scale molecular dynamics simulator with enhanced sampling algorithms for biomolecular and cellular simulations　　　　　　　　　　　　　　　
  Jaewoon Jung; Takaharu Mori; Chigusa Kobayashi; Yasuhiro Matsunaga; Takao Yoda; Michael Feig; Yuji Sugita
  WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE, Volume：5, Number：4, First page：310, Last page：323, Jul. 2015, [Reviewed]
  GENESIS (Generalized-Ensemble Simulation System) is a new software package for molecular dynamics (MD) simulations of macromolecules. It has two MD simulators, called ATDYN and SPDYN. ATDYN is parallelized based on an atomic decomposition algorithm for the simulations of all-atom force-field models as well as coarse-grained Go-like models. SPDYN is highly parallelized based on a domain decomposition scheme, allowing large-scale MD simulations on supercomputers. Hybrid schemes combining OpenMP and MPI are used in both simulators to target modern multicore computer architectures. Key advantages of GENESIS are (1) the highly parallel performance of SPDYN for very large biological systems consisting of more than one million atoms and (2) the availability of various REMD algorithms (T-REMD, REUS, multi-dimensional REMD for both all-atom and Go-like models under the NVT, NPT, NPAT, and NPT ensembles). The former is achieved by a combination of the midpoint cell method and the efficient three-dimensional Fast Fourier Transform algorithm, where the domain decomposition space is shared in real-space and reciprocal-space calculations. Other features in SPDYN, such as avoiding concurrent memory access, reducing communication times, and usage of parallel input/output files, also contribute to the performance. We show the REMD simulation results of a mixed (POPC/DMPC) lipid bilayer as a real application using GENESIS. GENESIS is released as free software under the GPLv2 licence and can be easily modified for the development of new algorithms and molecular models. (C) 2015 The Authors. WIREs Computational Molecular Science published by John Wiley & Sons, Ltd.
  WILEY-BLACKWELL, English, Scientific journal
  DOI：https://doi.org/10.1002/wcms.1220
  DOI ID：10.1002/wcms.1220, ISSN：1759-0876, eISSN：1759-0884, Web of Science ID：WOS:000356605600002
• Sequential data assimilation for single-molecule FRET photon-counting data　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga; Akinori Kidera; Yuji Sugita
  JOURNAL OF CHEMICAL PHYSICS, Volume：142, Number：21, First page：214115, Jun. 2015, [Reviewed]
  Data assimilation is a statistical method designed to improve the quality of numerical simulations in combination with real observations. Here, we develop a sequential data assimilation method that incorporates one-dimensional time-series data of smFRET (single-molecule Forster resonance energy transfer) photon-counting into conformational ensembles of biomolecules derived from "replicated" molecular dynamics (MD) simulations. A particle filter using a large number of "replicated" MD simulations with a likelihood function for smFRET photon-counting data is employed to screen the conformational ensembles that match the experimental data. We examine the performance of the method using emulated smFRET data and coarse-grained (CG) MD simulations of a dye-labeled polyproline-20. The method estimates the dynamics of the end-to-end distance from smFRET data as well as revealing that of latent conformational variables. The particle filter is also able to correct model parameter dependence in CG MD simulations. We discuss the applicability of the method to real experimental data for conformational dynamics of biomolecules. (C) 2015 AIP Publishing LLC.
  AMER INST PHYSICS, English, Scientific journal
  DOI：https://doi.org/10.1063/1.4921983
  DOI ID：10.1063/1.4921983, ISSN：0021-9606, eISSN：1089-7690, Web of Science ID：WOS:000355931800071
• Extended phase-space methods for enhanced sampling in molecular simulations: A review
  Hiroshi Fujisaki; Kei Moritsugu; Yasuhiro Matsunaga; Tetsuya Morishita; Luca Maragliano
  Frontiers in Bioengineering and Biotechnology, Volume：3, First page：125, 2015, [Reviewed]
  Molecular Dynamics simulations are a powerful approach to study biomolecular conformational changes or protein-ligand, protein-protein, and protein-DNA/RNA interactions. Straightforward applications, however, are often hampered by incomplete sampling, since in a typical simulated trajectory the system will spend most of its time trapped by high energy barriers in restricted regions of the configuration space. Over the years, several techniques have been designed to overcome this problem and enhance space sampling. Here, we review a class of methods that rely on the idea of extending the set of dynamical variables of the system by adding extra ones associated to functions describing the process under study. In particular, we illustrate the Temperature Accelerated Molecular Dynamics (TAMD), Logarithmic Mean Force Dynamics (LogMFD), and Multiscale Enhanced Sampling (MSES) algorithms. We also discuss combinations with techniques for searching reaction paths. We show the advantages presented by this approach and how it allows to quickly sample important regions of the free-energy landscape via automatic exploration.
  Frontiers Media S.A., English, Scientific journal
  DOI：https://doi.org/10.3389/fbioe.2015.00125
  DOI ID：10.3389/fbioe.2015.00125, ISSN：2296-4185, SCOPUS ID：84978048228
• Spatio-temporal hierarchy in the dynamics of a minimalist protein model　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga; Akinori Baba; Chun-Biu Li; John E. Straub; Mikito Toda; Tamiki Komatsuzaki; R. Stephen Berry
  JOURNAL OF CHEMICAL PHYSICS, Volume：139, Number：21, First page：215101, Dec. 2013, [Reviewed]
  A method for time series analysis of molecular dynamics simulation of a protein is presented. In this approach, wavelet analysis and principal component analysis are combined to decompose the spatio-temporal protein dynamics into contributions from a hierarchy of different time and space scales. Unlike the conventional Fourier-based approaches, the time-localized wavelet basis captures the vibrational energy transfers among the collective motions of proteins. As an illustrative vehicle, we have applied our method to a coarse-grained minimalist protein model. During the folding and unfolding transitions of the protein, vibrational energy transfers between the fast and slow time scales were observed among the large-amplitude collective coordinates while the other small-amplitude motions are regarded as thermal noise. Analysis employing a Gaussian-based measure revealed that the time scales of the energy redistribution in the subspace spanned by such large-amplitude collective coordinates are slow compared to the other small-amplitude coordinates. Future prospects of the method are discussed in detail. (C) 2013 AIP Publishing LLC.
  AMER INST PHYSICS, English, Scientific journal
  DOI：https://doi.org/10.1063/1.4834415
  DOI ID：10.1063/1.4834415, ISSN：0021-9606, eISSN：1089-7690, Web of Science ID：WOS:000328636400048
• Influence of Structural Symmetry on Protein Dynamics　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga; Ryotaro Koike; Motonori Ota; Jeremy R. H. Tame; Akinori Kidera
  PLOS ONE, Volume：7, Number：11, First page：e50011, Nov. 2012, [Reviewed]
  Structural symmetry in homooligomeric proteins has intrigued many researchers over the past several decades. However, the implication of protein symmetry is still not well understood. In this study, we performed molecular dynamics (MD) simulations of two forms of trp RNA binding attenuation protein (TRAP), the wild-type 11-mer and an engineered 12-mer, having two different levels of circular symmetry. The results of the simulations showed that the inter-subunit fluctuations in the 11-mer TRAP were significantly smaller than the fluctuations in the 12-mer TRAP while the internal fluctuations were larger in the 11-mer than in the 12-mer. These differences in thermal fluctuations were interpreted by normal mode analysis and group theory. For the 12-mer TRAP, the wave nodes of the normal modes existed at the flexible interface between the subunits, while the 11-mer TRAP had its nodes within the subunits. The principal components derived from the MD simulations showed similar mode structures. These results demonstrated that the structural symmetry was an important determinant of protein dynamics in circularly symmetric homooligomeric proteins.
  PUBLIC LIBRARY SCIENCE, English, Scientific journal
  DOI：https://doi.org/10.1371/journal.pone.0050011
  DOI ID：10.1371/journal.pone.0050011, ISSN：1932-6203, Web of Science ID：WOS:000311929800053
• Minimum Free Energy Path of Ligand-Induced Transition in Adenylate Kinase　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga; Hiroshi Fujisaki; Tohru Terada; Tadaomi Furuta; Kei Moritsugu; Akinori Kidera
  PLOS COMPUTATIONAL BIOLOGY, Volume：8, Number：6, First page：e1002555, Jun. 2012, [Reviewed]
  Large-scale conformational changes in proteins involve barrier-crossing transitions on the complex free energy surfaces of high-dimensional space. Such rare events cannot be efficiently captured by conventional molecular dynamics simulations. Here we show that, by combining the on-the-fly string method and the multi-state Bennett acceptance ratio (MBAR) method, the free energy profile of a conformational transition pathway in Escherichia coli adenylate kinase can be characterized in a high-dimensional space. The minimum free energy paths of the conformational transitions in adenylate kinase were explored by the on-the-fly string method in 20-dimensional space spanned by the 20 largest-amplitude principal modes, and the free energy and various kinds of average physical quantities along the pathways were successfully evaluated by the MBAR method. The influence of ligand binding on the pathways was characterized in terms of rigid-body motions of the lid-shaped ATP-binding domain (LID) and the AMP-binding (AMPbd) domains. It was found that the LID domain was able to partially close without the ligand, while the closure of the AMPbd domain required the ligand binding. The transition state ensemble of the ligand bound form was identified as those structures characterized by highly specific binding of the ligand to the AMPbd domain, and was validated by unrestrained MD simulations. It was also found that complete closure of the LID domain required the dehydration of solvents around the P-loop. These findings suggest that the interplay of the two different types of domain motion is an essential feature in the conformational transition of the enzyme.
  PUBLIC LIBRARY SCIENCE, English, Scientific journal
  DOI：https://doi.org/10.1371/journal.pcbi.1002555
  DOI ID：10.1371/journal.pcbi.1002555, ISSN：1553-734X, eISSN：1553-7358, DBLP ID：journals/ploscb/MatsunagaFTFMK12, PubMed ID：22685395, Web of Science ID：WOS:000305965300025
• 2B1412 Path sampling for small peptide systems using the Onsager-Machlup action method(Proteins:Structure & Function II:Theory, Aggregation,Oral Presentation,The 50th Annual Meeting of the Biophysical Society of Japan)　　　　　　　　　　　　　　　
  Fujisaki Hiroshi; Matsunaga Yasuhiro; Kidera Akinori
  Seibutsu Butsuri, Volume：52, First page：S40, 2012
  The Biophysical Society of Japan General Incorporated Association, English
  DOI：https://doi.org/10.2142/biophys.52.S40_2
  DOI ID：10.2142/biophys.52.S40_2, CiNii Articles ID：110009584700
• Non-Brownian Phase Space Dynamics of Molecules, the Nature of their Vibrational States, and Non-RRKM Kinetics　　　　　　　　　　　　　　　
  David M. Leitner; Yasuhiro Matsunaga; Chun-Biu Li; Tamiki Komatsuzaki; Akira Shojiguchi; Mikito Toda
  Advancing Theory for Kinetics and Dynamics of Complex, Many-Dimensional Systems: Clusters and Proteins, First page：83, Last page：122, Jul. 2011
  John Wiley {\&} Sons, Inc.
  DOI：https://doi.org/10.1002/9781118087817.ch3
  DOI ID：10.1002/9781118087817.ch3, ISSN：1934-4791, ORCID：121848864
• PROTEIN FUNCTIONAL MOTIONS: BASIC CONCEPTS AND COMPUTATIONAL METHODOLOGIES　　　　　　　　　　　　　　　
  Sotaro Fuchigami; Hiroshi Fujisaki; Yasuhiro Matsunaga; Akinori Kidera
  ADVANCING THEORY FOR KINETICS AND DYNAMICS OF COMPLEX, MANY-DIMENSIONAL SYSTEMS: CLUSTERS AND PROTEINS: ADVANCES IN CHEMICAL PHYSICS, VOL 145, Volume：145, First page：35, Last page：82, 2011, [Reviewed]
  WILEY-BLACKWELL, English, In book
  DOI：https://doi.org/10.1002/9781118087817.ch2
  DOI ID：10.1002/9781118087817.ch2, ISSN：0065-2385, Web of Science ID：WOS:000305145000004
• Cooperativity at different space and time scales in multiscale protein dynamics　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga; Chun-Biu Li; Tamiki Komatsuzaki
  PHYSICAL REVIEW E, Volume：82, Number：1, First page：016213, Jul. 2010, [Reviewed]
  A method proposed by Matsunaga et al. (Phys. Rev. Lett. 99, 238103 (2007) ] is applied to simple stochastic models and two model proteins composed of 46 amino beads with three different kinds of residues. The method, which is based on the combination of the principal component analysis and the finite size Lyapunov exponent, characterize the coarse-grained dynamics in different spatiotemporal hierarchies in protein dynamics. The application of the method to model proteins reveals that the low-indexed (large-variance) principal components carry less-divergent, regularized dynamics at the coarse-grained scales on a less-frustrated energy landscape, whereas this less-divergent nature is less pronounced for a protein model with a more frustrated energy landscape. It is also revealed that our technique can differentiate the collective motions on the projected principal component space inherent to the system and the apparent collective behavior which can appear even in high-dimensional stochastic systems.
  AMER PHYSICAL SOC, English, Scientific journal
  DOI：https://doi.org/10.1103/PhysRevE.82.016213
  DOI ID：10.1103/PhysRevE.82.016213, ISSN：1539-3755, eISSN：1550-2376, Web of Science ID：WOS:000280068000005
• Multivariate frequency domain analysis of protein dynamics　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga; Sotaro Fuchigami; Akinori Kidera
  JOURNAL OF CHEMICAL PHYSICS, Volume：130, Number：12, First page：124104, Mar. 2009, [Reviewed]
  Multivariate frequency domain analysis (MFDA) is proposed to characterize collective vibrational dynamics of protein obtained by a molecular dynamics (MD) simulation. MFDA performs principal component analysis (PCA) for a bandpass filtered multivariate time series using the multitaper method of spectral estimation. By applying MFDA to MD trajectories of bovine pancreatic trypsin inhibitor, we determined the collective vibrational modes in the frequency domain, which were identified by their vibrational frequencies and eigenvectors. At near zero temperature, the vibrational modes determined by MFDA agreed well with those calculated by normal mode analysis. At 300 K, the vibrational modes exhibited characteristic features that were considerably different from the principal modes of the static distribution given by the standard PCA. The influences of aqueous environments were discussed based on two different sets of vibrational modes, one derived from a MD simulation in water and the other from a simulation in vacuum. Using the varimax rotation, an algorithm of the multivariate statistical analysis, the representative orthogonal set of eigenmodes was determined at each vibrational frequency.
  AMER INST PHYSICS, English, Scientific journal
  DOI：https://doi.org/10.1063/1.3090812
  DOI ID：10.1063/1.3090812, ISSN：0021-9606, PubMed ID：19334805, Web of Science ID：WOS:000264775200007
• Anomalous diffusion in folding dynamics of minimalist protein landscape　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga; Chun-Biu Li; Tamiki Komatsuzaki
  PHYSICAL REVIEW LETTERS, Volume：99, Number：23, First page：238103, Dec. 2007, [Reviewed]
  A novel method is proposed to quantify collectivity at different space and time scales in multiscale dynamics of proteins. This is based on the combination of the principal component (PC) and the concept recently developed for multiscale dynamical systems called the finite size Lyapunov exponent. The method can differentiate the well-known apparent correlation along the low-indexed PCs in multidimensional Brownian systems from the correlated motion inherent to the system. As an illustration, we apply the method to a model protein of 46 amino beads with three different types of residues. We show how the motion of the model protein changes depending on the space scales and the choices of degrees of freedom. In particular, anomalous superdiffusion is revealed along the low-indexed PC in the unfolded state. The implication of superdiffusion in the process of folding is also discussed.
  AMER PHYSICAL SOC, English, Scientific journal
  DOI：https://doi.org/10.1103/PhysRevLett.99.238103
  DOI ID：10.1103/PhysRevLett.99.238103, ISSN：0031-9007, PubMed ID：18233416, Web of Science ID：WOS:000251451000072
• Topographical complexity of multidimensional energy landscapes　　　　　　　　　　　　　　　
  Gareth J. Rylance; Roy L. Johnston; Yasuhiro Matsunaga; Chun-Biu Li; Akinori Baba; Tamiki Komatsuzaki
  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Volume：103, Number：49, First page：18551, Last page：18555, Dec. 2006, [Reviewed]
  A scheme for visualizing and quantifying the complexity of multidimensional energy landscapes and multiple pathways is presented employing principal component-based disconnectivity graphs and the Shannon entropy of relative "sizes" of superbasins. The principal component-based disconnectivity graphs incorporate a metric relationship between the stationary points of the system, which enable us to capture not only the actual assignment of the superbasins but also the size of each superbasin in the multidimensional configuration space. The landscape complexity measure quantifies the degree of topographical complexity of a multidimensional energy landscape and tells us at which energy regime branching of the main path becomes significant, making the system more likely to be kinetically trapped in local minima. The path complexity measure quantifies the difficulty encountered by the system to reach a connected local minimum by the path in question, implying that the more significant the branching points along the path the more difficult it is to end up in the desired local minimum. As an illustrative example, we apply this analysis to two kinds of small model protein systems exhibiting a highly frustrated and an ideal funnel-like energy landscape.
  NATL ACAD SCIENCES, English, Scientific journal
  DOI：https://doi.org/10.1073/pnas.0608517103
  DOI ID：10.1073/pnas.0608517103, ISSN：0027-8424, PubMed ID：17132739, Web of Science ID：WOS:000242689800032
• Phase-space reaction network on a multisaddle energy landscape: HCN isomerization　　　　　　　　　　　　　　　
  CB Li; Y Matsunaga; M Toda; T Komatsuzaki
  JOURNAL OF CHEMICAL PHYSICS, Volume：123, Number：18, First page：184301, Nov. 2005, [Reviewed]
  By using the HCN/CNH isomerization reaction as an illustrative vehicle of chemical reactions on multisaddle energy landscapes, we give explicit visualizations of molecular motions associated with a straight-through reaction tube in the phase space inside which all reactive trajectories pass from one basin to another, with eliminating recrossing trajectories in the configuration space. This visualization provides us with a chemical intuition of how chemical species "walk along" the reaction-rate slope in the multidimensional phase space compared with the intrinsic reaction path in the configuration space. The distinct nonergodic features in the two different HCN and CNH wells can be easily demonstrated by a section of Poincare surface of section in those potential minima, which predicts in a priori the pattern of trajectories residing in the potential well. We elucidate the global phase-space structure which gives rise to the non-Markovian dynamics or the dynamical correlation of sequential multisaddle chemical reactions. The phase-space structure relevant to the controllability of the product state in chemical reactions is also discussed. (c) 2005 American Institute of Physics.
  AMER INST PHYSICS, English, Scientific journal
  DOI：https://doi.org/10.1063/1.2044707
  DOI ID：10.1063/1.2044707, ISSN：0021-9606, eISSN：1089-7690, PubMed ID：16292902, Web of Science ID：WOS:000233171300010
• How many dimensions are required to approximate the potential energy landscape of a model protein?　　　　　　　　　　　　　　　
  T Komatsuzaki; K Hoshino; Y Matsunaga; GJ Rylance; RL Johnston; DJ Wales
  JOURNAL OF CHEMICAL PHYSICS, Volume：122, Number：8, First page：84714, Feb. 2005, [Reviewed]
  A scheme to approximate the multidimensional potential energy landscape in terms of a minimal number of degrees of freedom is proposed using a linear transformation of the original atomic Cartesian coordinates. For one particular off-lattice model protein the inherent frustration can only be reproduced satisfactorily when a relatively large number of coordinates are employed. However, when this frustration is removed in a G (o) over bar -type model, the number of coordinates required is significantly lower, especially around the global potential energy minimum. To aid our interpretation of the results we consider modified disconnectivity graphs where a measure of the structural diversity and a metric relation between the stationary points are incorporated. (C) 2005 American Institute of Physics.
  AMER INST PHYSICS, English, Scientific journal
  DOI：https://doi.org/10.1063/1.1854123
  DOI ID：10.1063/1.1854123, ISSN：0021-9606, PubMed ID：15836084, Web of Science ID：WOS:000227372200074
• REGULARITY IN CHAOTIC TRANSITIONS ON MULTIBASIN LANDSCAPES　　　　　　　　　　　　　　　
  Tamiki Komatsuzaki; Kyoko Hoshino; Yasuhiro Matsunaga
  GEOMETRIC STRUCTURES OF PHASE SPACE IN MULTIDIMENSIONAL CHAOS: APPLICATIONS TO CHEMICAL REACTION DYNAMICS IN COMPLEX SYSTEMS, PT B, Volume：130, First page：257, Last page：313, 2005, [Reviewed]
  JOHN WILEY & SONS INC, English
  DOI：https://doi.org/10.1002/0471712531.ch17
  DOI ID：10.1002/0471712531.ch17, ISSN：0065-2385, Web of Science ID：WOS:000266721900008
• Multibasin dynamics in off-lattice minimalist protein landscapes　　　　　　　　　　　　　　　
  Y Matsunaga; KS Kostov; T Komatsuzaki
  JOURNAL OF PHYSICAL CHEMISTRY A, Volume：106, Number：45, First page：10898, Last page：10907, Nov. 2002, [Reviewed]
  We analyze time series of potential energy fluctuations and principal components at several temperatures for two kinds of off-lattice 46-bead models that have two distinctive energy landscapes. The less-frustrated "funnel" energy landscape brings about stronger nonstationary behavior of the potential energy fluctuations at the folding temperature than the other, rather frustrated energy landscape at the collapse temperature with a significant 1/f(alpha)(alpha approximate to 1.5) noise structure and a significant deviation of the Allan variance from the law of large numbers. The principal components are analyzed by an embedding nonlinear time-series analysis. The fast fluctuations with small amplitudes of similar to70-80% of the principal components cause the time series to become almost "random" in only 100 simulation steps. However, the stochastic feature of the principal components tends to be suppressed through a wide range of degrees of freedom at the transition temperature.
  AMER CHEMICAL SOC, English, Scientific journal
  DOI：https://doi.org/10.1021/jp025773j
  DOI ID：10.1021/jp025773j, ISSN：1089-5639, CiNii Articles ID：80015628398, Web of Science ID：WOS:000179180300023

• Analyses of Structure Changes and Free Energy of Sarco/Endoplasmic Reticulum Ca²⁺-ATPase
  Chigusa KOBAYASHI; Yasuhiro MATSUNAGA; Jaewoon JUNG; Yuji SUGITA
  Seibutsu Butsuri, Volume：62, Number：5, First page：298, Last page：300, Nov. 2022, [Reviewed], [Invited]
  Biophysical Society of Japan
  DOI：https://doi.org/10.2142/biophys.62.298
  DOI ID：10.2142/biophys.62.298, ISSN：0582-4052, eISSN：1347-4219
• How Can We Describe the Conformational Change of Proteins?-Advances in Path Sampling Techniques for Biomolecules　　　　　　　　　　　　　　　
  松永康佑; 森次圭; 藤崎弘士
  日本物理学会誌, Volume：76, Number：11, 2021
  ISSN：0029-0181, J-Global ID：202102210518233099
• Kinetics of conformational changes of proteins calculated by manifold learning　　　　　　　　　　　　　　　
  藤崎弘士; 森次圭; 松永康佑; 山本典史; 末谷大道
  日本物理学会講演概要集(CD-ROM), Volume：76, Number：2, 2021
  ISSN：2189-079X, J-Global ID：202202218685875116
• 重み付きアンサンブル法を用いたタンパク質の構造変化とキネティックスの計算　　　　　　　　　　　　　　　
  藤崎弘士; 森次圭; 松永康佑
  Volume：74, Number：2, 2019
  ISSN：2189-079X, J-Global ID：202002216136411679
• 重み付きアンサンブル法による生体分子の構造変化ダイナミクスの計算　　　　　　　　　　　　　　　
  藤崎弘士; 森次圭; 松永康佑
  Volume：33rd, 2019
  J-Global ID：202002276357760426
• スーパーコンピューター「京」によって解明された多剤排出トランスポーターの薬剤排出機構　　　　　　　　　　　　　　　
  松永 康佑
  Volume：76, Number：5, First page：410, Last page：412, 2018, [Invited]
  Japanese
• 実験と計算の時間スケールが重なったことで見えてきたこと　　　　　　　　　　　　　　　
  松永 康佑
  Nov. 2016, [Invited]
  Japanese
• On the Special Topic "Conformational Fluctuations and Dynamics of Biomolecules : Statistical Analysis of Computer Simulation and Experimental Data"　　　　　　　　　　　　　　　
  伊庭 幸人; 藤崎 弘士; 松永 康佑
  統計数理, Volume：62, Number：2, First page：163, Last page：170, Dec. 2014
  要旨なし生体高分子の揺らぎとダイナミクス－シミュレーションと実験の統計解析－その他・前書き
  統計数理研究所, Japanese
  ISSN：0912-6112, CiNii Articles ID：40020359216
• Conformational Transition Pathways in Proteins Explored by the String Method　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga
  統計数理, Volume：62, Number：2, First page：285, Last page：299, 2014, [Reviewed], [Invited]
  要旨あり生体高分子の揺らぎとダイナミクス－シミュレーションと実験の統計解析－研究詳解
  Japanese
  DOI：https://doi.org/10.11436/mssj.16.29
  DOI ID：10.11436/mssj.16.29, ISSN：0912-6112, CiNii Articles ID：120006020808
• ストリング法によるタンパク質構造変化の解析　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga
  Ensemble, Volume：16, Number：1, First page：29, Last page：35, Jan. 2014, [Reviewed], [Invited]
  Japanese
  DOI：https://doi.org/10.11436/mssj.16.29
  DOI ID：10.11436/mssj.16.29, ISSN：1884-6750, CiNii Articles ID：40019989626
• 27aXZC-3 Path sampling of small peptides using the Onsager-Machlup action　　　　　　　　　　　　　　　
  Fujisaki Hiroshi; Matsunaga Yasuhiro; Kidera Akinori
  Meeting Abstracts of the Physical Society of Japan, Volume：68, Number：0, First page：432, Last page：432, 2013
  The Physical Society of Japan (JPS), Japanese
  ISSN：1342-8349, CiNii Articles ID：110009643989, CiNii Books ID：AA11439205
• Conformational Transition Pathways of Adenylate Kinase Explored by the String Method　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga; Hiroshi Fujisaki; Tohru Terada; Akinori Kidera
  BIOPHYSICAL JOURNAL, Volume：102, Number：3, First page：733A, Last page：733A, Jan. 2012
  CELL PRESS, English, Summary international conference
  ISSN：0006-3495, Web of Science ID：WOS:000321561205178
• NON-BROWNIAN PHASE SPACE DYNAMICS OF MOLECULES, THE NATURE OF THEIR VIBRATIONAL STATES, AND NON-RRKM KINETICS
  David M. Leitner; Yasuhiro Matsunaga; Chun-Biu Li; Tamiki Komatsuzaki; Akira Shojiguchi; Mikito Toda
  ADVANCING THEORY FOR KINETICS AND DYNAMICS OF COMPLEX, MANY-DIMENSIONAL SYSTEMS: CLUSTERS AND PROTEINS: ADVANCES IN CHEMICAL PHYSICS, VOL 145, Volume：145, First page：83, Last page：122, 2011
  WILEY-BLACKWELL, English
  ISSN：0065-2385, SCOPUS ID：84861908071, Web of Science ID：WOS:000305145000005
• Supercomputing 09 参加報告書 (SC09レポート)　　　　　　　　　　　　　　　
  松永康佑
  2009, [Invited]
  Japanese, Meeting report
• F1-4 Investigating collective protein dynamics by molecular dynamics simulation and time-series analysis　　　　　　　　　　　　　　　
  MATSUNAGA Yasuhiro; KIDERA Akinori
  The Computational Mechanics Conference, Volume：2008, Number：21, First page：7, Last page：8, 01 Nov. 2008
  The Japan Society of Mechanical Engineers, Japanese
  ISSN：1348-026X, CiNii Articles ID：110008701614, CiNii Books ID：AA1190257X
• Polymers and Chaos: Anomalous Diffusion and Hierarchical Regularity　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga; Tamiki Komatsuzaki
  Kobunshi, Volume：57, Number：2, First page：58, Last page：61, 2008, [Invited]
  A novel method is proposed which quantifies collectivity emerging at coarse-grained space and time scales in multi-scale protein dynamics. This is based on the combination of the principal component (PC) and the finite size Lyapunov exponent (FSLE). This method can systematically assess the coarse-grained dynamics at different scales in the reduced PC space. As an illustrative vehicle, we apply the method to a model protein composed of 46 amino beads with three different types of residues. We show how the motion of the model protein changes depending on the space scales and the choice of degrees of freedom. In particular, anomalous superdiffusion is revealed along the first PC in the unfolded state. The implication of the existence of superdiffusion in the folding dynamics is discussed. © 2008, The Society of Polymer Science, Japan. All rights reserved.
  社団法人 高分子学会, English
  DOI：https://doi.org/10.1295/kobunshi.57.58
  Scopus：https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85024454719&origin=inward
  Scopus Citedby：https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85024454719&origin=inward
  DOI ID：10.1295/kobunshi.57.58, ISSN：0454-1138, CiNii Articles ID：10021118818, SCOPUS ID：85024454719
• 19aTC-10 Collectivity at Different Space and Time Scales in Multiscale Protein Dynamics　　　　　　　　　　　　　　　
  Matsunaga Yasuhiro; Li Chun-Biu; Komatsuzaki Tamiki
  Meeting Abstracts of the Physical Society of Japan, Volume：62, Number：0, First page：337, Last page：337, 2007
  The Physical Society of Japan, Japanese
  ISSN：1342-8349, CiNii Articles ID：110007193386, CiNii Books ID：AA11439205
• タンパク質エネルギー地形における構造多様性と多次元エネルギー地形の新しい可視化手法 (複雑な多谷ポテンシャルエネルギー面上で生起する動力学諸問題--タンパク質とその周辺)　　　　　　　　　　　　　　　
  星野 恭子; 松永 康佑; Lylance Gareth J; Johnston Roy L; Wales David J; 小松崎 民樹
  Volume：86, Number：1, First page：117, Last page：122, Apr. 2006
  この論文は国立情報学研究所の電子図書館事業により電子化されました。
  Japanese
  ISSN：0525-2997, J-Global ID：200902246619602529, CiNii Articles ID：110004799178
• 1P060 Chaotic time series analysis of collective motions in proteins　　　　　　　　　　　　　　　
  Matsunaga Y; Biu Li Chun; Komatsuzaki T
  Seibutsu Butsuri, Volume：45, Number：0, First page：S46, 2005
  一般社団法人 日本生物物理学会, Japanese
  DOI：https://doi.org/10.2142/biophys.45.S46_4
  DOI ID：10.2142/biophys.45.S46_4, ISSN：0582-4052, CiNii Articles ID：110004571041
• タンパク質エネルギー地形における自由度の縮約化と時系列解析　　　　　　　　　　　　　　　
  星野恭子; 松永康佑; MILLER Mark A.; WALES David J.; 小松崎民樹
  Volume：2004, 2004
  J-Global ID：200902271819526465
• A coarse-graining of energy landscape of proteins - Structural stability of the most stable states
  K Hoshino; Y Matsunaga; M Miller; DJ Wales; T Komatsuzaki
  SLOW DYNAMICS IN COMPLEX SYSTEMS, Volume：708, First page：344, Last page：345, 2004, [Reviewed]
  The minimal sets of degrees of freedom, to persist the multidimensional topographical feature are investigated for the funnel, and frustrated energy landscapes of proteins. The robustness of local energy topographies near the global energy minimum structures against a perturbation is also discussed.
  AMER INST PHYSICS, English
  ISSN：0094-243X, Web of Science ID：WOS:000222360700116
• Protein folding dynamics: ergodic behavior in principal component space
  Y Matsunaga; T Komatsuzaki
  SLOW DYNAMICS IN COMPLEX SYSTEMS, Volume：708, First page：342, Last page：343, 2004, [Reviewed]
  Using a novel method for determining the time scale for the self-averaging of properties of many body systems, the effective ergodic behavior of a coarse-grained protein model was investigated in terms of both the chemical characters and the principal components. The ergodic behavior was examined in detail with a focus on the time scale needed to obtain effective ergodicity.
  AMER INST PHYSICS, English
  ISSN：0094-243X, Web of Science ID：WOS:000222360700115
• Hierarchical regularity in multi-basin dynamics on protein landscapes
  Y Matsunaga; KS Kostov; T Komatsuzaki
  SLOW DYNAMICS IN COMPLEX SYSTEMS, Volume：708, First page：302, Last page：305, 2004, [Reviewed]
  We analyze time series of potential energy fluctuations and principal components at several temperatures for two kinds of off-lattice 46-bead models that have two distinctive energy landscapes. The less-frustrated "funnel" energy landscape brings about stronger nonstationary behavior of the potential energy fluctuations at the folding temperature than the other, rather frustrated energy landscape at the collapse temperature. By combining principal component analysis with an embedding nonlinear time-series analysis, it is shown that the fast fluctuations with small amplitudes of 70-80% of the principal components cause the time series to become almost "random" in only 100 simulation steps. However, the stochastic feature of the principal components tends to be suppressed through a wide range of degrees of freedom at the transition temperature.
  AMER INST PHYSICS, English
  ISSN：0094-243X, Web of Science ID：WOS:000222360700098
• 蛋白質フォールディングのダイナミックス : 異常拡散と動的相関(修士論文(2002年度))　　　　　　　　　　　　　　　
  松永 康佑
  Volume：81, Number：4, First page：571, Last page：592, Jan. 2004
  タンパク質の粗視化モデルに対して様々な温度で分子動力学計算を行い、得られた時系列を主に非線形時系列解析の手法を用いて解析した。調べたモデルは46アミノ酸残基からなり、天然構造として4つのstrandを持つβ-barrel型をとるモデルであり、その派生型であるファネル型に近いGo^^-likeモデルも併せて解析した。ポテンシャルエネルギーの揺らぎのアラン分散やパワースペクトルによる解析では、フラストレーションがより小さいエネルギー地形を有するGo^^-likeモデルではその折れたたみの転移温度においてオリジナルモデルよりも長い時間スケールに渡って、より強い非定常性を示し、白色ノイズ→1/fノイズへの、より先鋭な転移を伴うことが判明した。また、埋め込み解析による運動の次元性については、転移温度での揺らぎの大きい数10成分の埋め込み次元が、他の温度領域に比べて顕著に小さいことが判明した。これらの結果は総合的に、転移温度付近における低次元な長時間記憶を持つダイナミックスの存在を示唆している。
  Japanese
  ISSN：0525-2997, CiNii Articles ID：110006409265, CiNii Books ID：AN0021948X
• Extracting dynamical information about protein folding from time series analysis.　　　　　　　　　　　　　　　
  K Kostov; M Toda; Y Matsunaga; T Komatsuzaki
  ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Volume：226, First page：U427, Last page：U427, Sep. 2003
  AMER CHEMICAL SOC, English, Summary international conference
  ISSN：0065-7727, Web of Science ID：WOS:000187062401978
• 生体分子時系列情報からの状態空間の再構成と主成分解析　　　　　　　　　　　　　　　
  星野恭子; 松永康佑; 小松崎民樹
  Volume：2003, 2003
  J-Global ID：200902281174160580
• Non-stationarity and non-Markovianity of foldings in small proteins　　　　　　　　　　　　　　　
  Hoshino Kyoko; Matsunaga Yasuhiro; Koga Nobuyasu; Takada Shoji; Komatsuzaki Tamiki
  Meeting Abstracts of the Physical Society of Japan, Volume：58, Number：0, First page：334, Last page：334, 2003
  The Physical Society of Japan, Japanese
  ISSN：1342-8349, CiNii Articles ID：110002215733, CiNii Books ID：AA11439205
• Protein Folding Dynamics : dynamical effect of solvents　　　　　　　　　　　　　　　
  Matsunaga Yasuhiro; Komatsuzaki Tamiki
  Meeting Abstracts of the Physical Society of Japan, Volume：58, Number：0, First page：356, Last page：356, 2003
  The Physical Society of Japan, Japanese
  ISSN：1342-8349, CiNii Articles ID：110002216019, CiNii Books ID：AA11439205
• Coherence emerging at a Coarse-Grained Scale in Protein foldings　　　　　　　　　　　　　　　
  Komatsuzaki Tamiki; Matsunaga Yasuhiro; Toda Mikito
  Meeting Abstracts of the Physical Society of Japan, Volume：58, Number：0, First page：356, Last page：356, 2003
  The Physical Society of Japan, Japanese
  ISSN：1342-8349, CiNii Articles ID：110002216023, CiNii Books ID：AA11439205
• Dynamics of Protein Folding : Abnormal Diffusion and Hierarchical Regularity　　　　　　　　　　　　　　　
  KOMATSUZAKI Tamiki; MATSUNAGA Yasuhiro
  Biophysics, Volume：42, Number：6, First page：285, Last page：289, Nov. 2002, [Reviewed], [Invited]
  日本生物物理学会, Japanese
  DOI ID：10.2142/biophys.42.285, ISSN：0582-4052, J-Global ID：200902167987891002, CiNii Articles ID：110001151651
• 蛋白質折れ畳みダイナミックスにおける階層的規則性(複雑な多谷ポテンシャルエネルギー面上で生起する動力学的諸問題-力学的決定性と統計性の中間領域を探る(第2回)-,研究会報告)　　　　　　　　　　　　　　　
  松永 康佑
  Volume：78, Number：4, First page：457, Last page：462, 2002
  Japanese
  ISSN：0525-2997, CiNii Articles ID：110006408597, CiNii Books ID：AN0021948X
• タンパク質フォールディングのダイナミックス-異常拡散と動的相関　　　　　　　　　　　　　　　
  松永康佑; 小松崎民樹
  Volume：3rd, 2002
  J-Global ID：200902145982107520
• Off-Latticeビーズモデルに基づく蛋白質ダイナミックス 非定常性,非マルコフ性,および次元性　　　　　　　　　　　　　　　
  松永康佑; KOSTOV K; 小松崎民樹
  Volume：2002, 2002
  J-Global ID：200902193694028530
• 1K1715 Multi-Basin Dynamics in Off-Lattice Minimalist Protein Landscapes　　　　　　　　　　　　　　　
  Matsunaga Y; Komatsuzaki T
  Seibutsu Butsuri, Volume：42, Number：2, First page：S66, 2002
  一般社団法人 日本生物物理学会, Japanese
  DOI：https://doi.org/10.2142/biophys.42.S66_2
  DOI ID：10.2142/biophys.42.S66_2, ISSN：0582-4052, CiNii Articles ID：110007133016
• Cooperative Motions in Proteins: Randomness and Regularity.　　　　　　　　　　　　　　　
  松永康佑; 小松崎民樹
  日本化学会講演予稿集, Volume：79th, Number：1, 2001
  ISSN：0285-7626, J-Global ID：200902114129687107
• Hierarchical Regularity in Protein Folding Dynamics.　　　　　　　　　　　　　　　
  松永康佑; 小松崎民樹
  分子構造総合討論会講演要旨集, Volume：2001, 2001
  J-Global ID：200902132582752490
• Hierarchical Reularity and Energy Landscape in Protein Folding Dynamics　　　　　　　　　　　　　　　
  Matsunaga Yasuhiro; Komatsuzaki Tamiki
  Meeting Abstracts of the Physical Society of Japan, Volume：56, Number：0, First page：272, Last page：272, 2001
  The Physical Society of Japan, Japanese
  ISSN：1342-8349, CiNii Articles ID：110002025284, CiNii Books ID：AA11439205

• Protein Functional Motions: Basic Concepts and Computational Methodologies　　　　　　　　　　　　　　　
  S. Fuchigami; H. Fujisaki; Y. Matsunaga; A. Kidera
  Advances in Chemical Physics Vol. 145, page 35-82 (2011), 2011
• Non-Brownian Phase Space Dynamics of Molecules, the Nature of their Vibrational States, and non-RRKM Kinetics　　　　　　　　　　　　　　　
  D. M. Leitner; Y. Matsunaga; C.-B. Li; T. Komatsuzaki; A. Shojiguchi; M. Toda
  Advances in Chemical Physics Vol. 145 page 83-122 (2011), 2011
• Molecular Dynamics Simulation of Proteins: Two Models of Anharmonic Dynamics　　　　　　　　　　　　　　　
  A. Kidera; K. Moristugu; Y. Matsunaga; H. Fujisaki
  Proteins: Energy, Heat and Signal Flow, Chapter 5, p107-127 (2009), CRC Press., 2009

• Energetics and conformational pathways of functional rotation in the multidrug transporter AcrB　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga
  Sep. 2018, [Invited]
  English
• 機械学習を用いた計測とシミュレーションの統合によるタンパク質動態解析　　　　　　　　　　　　　　　
  松永 康佑
  Feb. 2018, [Invited]
  Japanese
• ストリング法による多剤排出トランスポーターAcrBの機能ダイナミクス解析　　　　　　　　　　　　　　　
  松永 康佑
  Jan. 2018, [Invited]
• 機械学習を用いた計測とシミュレーションの統合によるタンパク質動態解析　　　　　　　　　　　　　　　
  松永 康佑
  Nov. 2017, [Invited]
  Japanese
• 機械学習を用いた1分子計測とシミュレーションの統合とタンパク質動態解析　　　　　　　　　　　　　　　
  松永 康佑
  Sep. 2017, [Invited]
• Integrative modeling of protein folding dynamics from experiments and simulation　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga
  Telluride Workshop on “The Complexity of Dynamics and Kinetics from Single Molecules to Cells” Telluride, Colorado USA, Jun. 2017, [Invited]
  English
• Functional dynamics of multidrug transporter AcrB studied by string method　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga
  Mar. 2017, [Invited]
  English
• Drug extrusion mechanism of the multidrug transporter AcrB studied by molecular dynamics simulation　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga
  Mar. 2017, [Invited]
• Markov state modeling of protein folding dynamics by combining single-molecule experiments and simulations　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga
  Simulations Encounter with Data Science, Institute of Statistical Mathematics, Tokyo, Japan, Mar. 2017, [Invited]
• シミュレーションと実験を統合したモデリングで見えてきた生体分子の動態　　　　　　　　　　　　　　　
  松永 康佑
  Dec. 2016, [Invited]
• タンパク質構造変化における反応自由度探索法　　　　　　　　　　　　　　　
  松永 康佑
  Oct. 2016, [Invited]
• 生体分子におけるデータ同化　　　　　　　　　　　　　　　
  松永 康佑
  Oct. 2016, [Invited]
• 1分子FRETデータと分子動力学シミュレーションによるタンパク質ダイナミクス解析　　　　　　　　　　　　　　　
  松永 康佑
  Jun. 2016, [Invited]
• 1分子FRETデータと分子動力学シミュレーションによるタンパク質ダイナミクス解析　　　　　　　　　　　　　　　
  松永 康佑
  Jun. 2016, [Invited]
• Drug extrusion mechanism of multidrug transporter AcrB studied by the string method　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga
  Sep. 2015, [Invited]
• Drug extrusion mechanism of multidrug transporter AcrB studied by molecular dynamics simulations　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga
  Rare Event Sampling and Related Topics II, Institute of Statistical Mathematics, Tokyo, Japan, Mar. 2015, [Invited]
  English
• 最小自由エネルギー経路探索法による多剤排出トランスポーターの薬剤排出機構の解明　　　　　　　　　　　　　　　
  松永 康佑
  Oct. 2014, [Invited]
  Japanese
• Finding Conformational Transition Pathways in Biomolecules with the String Method and Sequential Data Assimilation　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga
  Rare Event Sampling and Related Topics I, Institute of Statistical Mathematics, Tokyo, Japan, Mar. 2014, [Invited]
  English
• Sequential data assimilation of single-molecule FRET photon-counting data by using molecular dynamics simulations　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga
  Workshop on Molecular Simulations of Biophysics and Biochemistry, RIKEN AICS, Kobe, Japan, Nov. 2013, [Invited]
  English
• 生体分子シミュレーション研究のGPGPUによる加速　　　　　　　　　　　　　　　
  松永 康佑
  Jun. 2013, [Invited]
  Japanese
• 有限温度ストリング法によるアデニル酸キナーゼの最小自由エネルギー経路探索　　　　　　　　　　　　　　　
  松永 康佑
  Sep. 2012, [Invited]
  Japanese
• タンパク質の構造変化サンプリング - ストリング法とデータ同化　　　　　　　　　　　　　　　
  松永 康佑
  Mar. 2012, [Invited]
  Japanese
• 分子動力学シミュレーションの基礎と応用　　　　　　　　　　　　　　　
  松永 康佑
  Sep. 2011, [Invited]
  Japanese
• ストリング法によるタンパク質構造変化解析　　　　　　　　　　　　　　　
  松永 康佑
  Jun. 2011, [Invited]
  Japanese
• マルチコピーシミュレーションによるタンパク質構造サンプリング　　　　　　　　　　　　　　　
  松永康佑; 寺田透; 森次圭; 古田忠臣; 藤崎弘士; 木寺詔紀
  Feb. 2011, [Invited]
  Japanese
• パスサンプリングによるタンパク質構造変化解析　　　　　　　　　　　　　　　
  松永 康佑
  Dec. 2009, [Invited]
  Japanese
• 逐次モンテカルロ法で探るタンパク質ダイナミックス　　　　　　　　　　　　　　　
  松永 康佑
  May 2009, [Invited]
  Japanese
• 生体分子構造転移ダイナミックスの時系列解析　　　　　　　　　　　　　　　
  松永 康佑
  Mar. 2004, [Invited]
  Japanese

• PROTEIN SCIENCE SOCIETY OF JAPAN
• THE BIOPHYSICAL SOCIETY OF JAPAN

• MDToolbox.jl　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga
  2018 - Present, [Software]
  MDToolbox: A Julia package for statistical analysis of molecular dynamics trajectories
• GENESIS: Generalized Ensemble Simulation System　　　　　　　　　　　　　　　
  Y. Sugita; J. Jung; T. Mori; C. Kobayashi; Y. Matsunaga; T. Imai; T. Yoda
  2015 - Present, [Software]
• MDToolbox　　　　　　　　　　　　　　　
  Yasuhiro Matsunaga
  2012 - Present, [Software]
  MDToolbox: A MATLAB/Octave toolbox for statistical analysis of molecular dynamics trajectories
• プレスリリース 機械学習を用いたシミュレーションと実験計測データの融合　　　　　　　　　　　　　　　
  2018, [Others]
• プレスリリース 京コンピュータを用いた多剤排出トランスポータAcrBの薬剤排出メカニズムの解明　　　　　　　　　　　　　　　
  2018, [Others]
• プレスリリース 超並列分子動力学計算ソフトウェア「GENESIS」を開発　　　　　　　　　　　　　　　
  2015, [Others]
• mu2lib　　　　　　　　　　　　　　　
  [Software]

• エンドツーエンド微分可能なアプローチによる実験と生体分子モデリングの融合　　　　　　　　　　　　　　　
  28 Feb. 2024 - 31 Mar. 2026
  Grant amount(Total)：11830000, Direct funding：9100000, Indirect funding：2730000
  Grant number：23K28102
• タイリング理論と分子科学の協働によるウイルス外殻構造の新たな設計原理の探究　　　　　　　　　　　　　　　
  30 Jun. 2023 - 31 Mar. 2026
  Grant amount(Total)：6500000, Direct funding：5000000, Indirect funding：1500000
  Grant number：23K18105
• Integration of experiments and biomolecular modeling through end-to-end differentiable approaches　　　　　　　　　　　　　　　
  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), 01 Apr. 2023 - 31 Mar. 2026
  Saitama University
  Grant amount(Total)：18460000, Direct funding：14200000, Indirect funding：4260000
  Grant number：23H03412
• タイリングによるウイルス外殻のボトムアップ設計　　　　　　　　　　　　　　　
  30 Jul. 2020 - 31 Mar. 2023
  Grant amount(Total)：6500000, Direct funding：5000000, Indirect funding：1500000
  Grant number：20K21380
• 生体分子動態解析のためのデータ同化基盤の開発と応用　　　　　　　　　　　　　　　
  JST, PRESTO, Oct. 2016 - Mar. 2020
  Yasuhiro Matsunaga, Principal investigator
  Competitive research funding
• 生体分子ダイナミクスのマルコフ状態モデルを構築するための効率的な構造サンプリング手法の開発　　　　　　　　　　　　　　　
  Apr. 2018 - Mar. 2019
  Principal investigator
  Competitive research funding
• バンディットアルゴリズムに基づいた生体分子の効率的な構造サンプリング法の開発　　　　　　　　　　　　　　　
  Apr. 2017 - Mar. 2018
  Principal investigator
  Competitive research funding
• シミュレーションと実験によるタンパク質ダイナミクスの統合モデリング　　　　　　　　　　　　　　　
  Apr. 2017 - Jun. 2017
  Principal investigator
  Competitive research funding
• 大規模分子シミュレーションと実験の融合によるタンパク質ダイナミクス解析　　　　　　　　　　　　　　　
  Apr. 2016 - Mar. 2017
  Principal investigator
  Competitive research funding
• パスサンプリングによる1分子FRET光子計数データのモデリング　　　　　　　　　　　　　　　
  Apr. 2014 - Mar. 2016
  Principal investigator
  Competitive research funding
• パスサンプリングによるタンパク質構造変化解析基盤の構築　　　　　　　　　　　　　　　
  Apr. 2011 - Mar. 2014
  Principal investigator
  Competitive research funding
• データ同化技術を用いた1分子FRET計測融合シミュレーションによるタンパク質動態の解明　　　　　　　　　　　　　　　
  Apr. 2012 - Mar. 2013
  Principal investigator
  Competitive research funding
• Statistical analysis of conformational changes of proteins　　　　　　　　　　　　　　　
  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (B), 2012 - 2012
  MATSUNAGA YASUHIRO, Principal investigator
  Grant amount(Total)：2860000, Direct funding：2200000, Indirect funding：660000
  With the help of recent advances in computer hardware and software, it is becoming possible to simulate functionally relevant conformational changes of biomolecules. On the other hand, however, the amount of simulation data is rapidly increasing and it is becoming difficult to treat such large amount of data without statistical analysis. In this study, we have developed a framework for the statistical analysis of molecular dynamics simulation data. The developed framework was successfully applied to conformational change data of two cases: (i) The most slowest degrees of freedom (involving the P-loop and a hinge region) in Adenylate Kinase was identified from 9 microseconds simulation data. (ii) Free energy differences along the conformational change pathways of multidrug transporter AcrB was successfully evaluated.
  Competitive research funding, Grant number：24770159
• 生体分子系の構造転移ダイナミックスに対する非線形時系列解析理論の構築　　　　　　　　　　　　　　　
  Apr. 2004 - Mar. 2006
  Principal investigator
  Competitive research funding, Grant number：04J04006