Centers & Labs

RIKEN Center for Computational Science

Computational Structural Biology Research Team

Team Leader: Florence Tama (Ph.D.)
Florence  Tama(Ph.D.)

Biological complexes, structured ensembles of proteins or proteins/nucleic acids, perform many vital cellular functions, such as gene transcription, protein synthesis or regulation of cellular transport, and dysfunctions of those result in severe diseases. In order to understand diseases and develop treatments, the functional mechanisms of these biological complexes need to be elucidated. A crucial step in this process is the characterization of the structure and dynamics of these complexes. As large complexes are difficult to study by X-ray crystallography, alternative low-resolution experimental techniques such as cryo-electron microscopy, small angle X-ray scattering and fluorescence resonance energy transfer are often used to characterize their conformational states. Additionally, new experimental developments of X-ray Free Electron Lasers (XFEL, such as in SPring 8, RIKEN) should provide structural information close to atomic resolution. Our goal is to develop computational methods to obtain atomic level description of the functional states of biological complexes. Such methods will rely on the integration of various experimental data such as high resolution X-ray crystallography, lower resolution cryo-EM and emerging near atomic resolution XFEL with computational modeling through high performance computing such as with the supercomputers K and Fugaku. In addition, we aim to collaborate with experimental groups and the pharmaceutical industry to elucidate functional mechanism of biological systems.

Main Research Field

Complex systems

Related Research Fields

Biological Sciences

Keywords

  • Modeling
  • structure
  • function
  • dynamics
  • low-resolution

Selected Publications

  1. T. Nagai, F. Tama & O. Miyashita.:
    "Cryo-cooling effect on DHFR crystal studied by replica-exchange molecular dynamics simulations"
    Biophysical J. 116(3):395-405 (2019).
  2. T. Mori, M. Kulik, O. Miyashita, J. Jung, F. Tama and Y. Sugita.:
    "Acceleration of cryo-EM flexible fitting by efficient space partitioning for large biomolecular systems"
    Structure 27(1):161-174. (2019).
  3. A. Srivastava, F. Tama, D. Kohda & O. Miyashita.:
    "Computational Investigation of the Conformational Dynamics in Tom20-Mitochondrial Presequence Tethered Complexes"
    Proteins 87(1):81-90. (2019).
  4. T. Nagai, Y. Mochizuki, Y. Joti, F. Tama & O. Miyashita.:
    "Gaussian mixture model for coarse-grained modeling from XFEL"
    Optics Express 26(20):26734-26749. (2018).
  5. S. P. Tiwari, F. Tama & O. Miyashita.:
    "Searching for 3D structural models from a library of biological shapes using a few 2D experimental images"
    BMC Bioinformatics 19:320. (2018).
  6. M. Nakano, O. Miyashita, S. Jonic, A. Tokuhisa, F. Tama.:
    "Single-particle XFEL 3D Reconstruction of Ribosome-size Particles based on Fourier Slice Matching: Requirements to Reach Subnanometer Resolution"
    J. Synchrotron Rad. 25:1010-1021. (2018).
  7. O. Miyashita, C. Kobayashi, T. Mori, Y. Sugita, F. Tama.:
    "Flexible Fitting to Cryo-EM Density Map using Ensemble Molecular Dynamics Simulations"
    J. Comp. Chem. 38:1447-1461. (2017).
  8. A. Tokuhisa, S. Jonic, F. Tama and O. Miyashita.:
    "Hybrid Approach for Structural Modeling of Biological Systems from X-ray Free Electron Laser Diffraction Patterns"
    J. Struct. Biol. 194(3):325-336 (2016).
  9. M. Gallagher-Jones, Y. Bessho, S. Kim, J. Park, S. Kim, D. Nam, C. Kim, Y. Kim, Y. Noh do, O. Miyashita, F. Tama, Y. Joti, T. Kameshima, T. Hatsui, K. Tono, Y. Kohmura, M. Yabashi, SS. Hasnain, T. Ishikawa, C. Song.:
    "Macromolecular structures probed by combining single-shot free-electron laser diffraction with synchrotron coherent X-ray imaging"
    Nature Commun. 2:5:3798. (2014).
  10. Q Jin, CO Sorzano, JM de la Rosa-Trevín, JR Bilbao-Castro, R. Núñez-Ramírez, O. Llorca , F. Tama, S. Jonić.:
    "Iterative elastic 3D-to-2D alignment method using normal modes for studying structural dynamics of large macromolecular complexes"
    Structure 22:496-506. (2014).

Lab Members

Principal Investigator

Florence Tama
Team Leader

Core Members

Miki Nakano
Postdoctoral Researcher
Sandhya Tiwari
Postdoctoral Researcher