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Theoretical and Computational Molecular Science OKAZAKI Group

Location: Myoudaiji, South Laboratory Bldg. Room 419
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Theoretical Biophysics, Molecular Motors, Molecular Simulations

Functional Dynamics of Biomolecular Machines Revealed by Theoretical Methods

Functional dynamics plays an important role when biomolecular machines fulfill their functions. For example, motor proteins walk on the rail or rotate relative to the stator by using ATP hydrolysis energy. Transporter proteins transport their substrates across the membrane by changing their conformation between inward-open and outward-open conformations. We aim to understand design principles of these precise, yet dynamic nano-machines developed by nature.

Functional dynamics of biomolecular machines involve wide spectrum of intricate motions. In order to understand such dynamics, we need a multiscale approach to cover full range of these motions. Conventional atomistic molecular dynamics simulations alone cannot cover millisecond-long functional dynamics, especially for a large system like biomolecular machines. Thus, we use both atomistic and coarse-grained molecular simulations, as well as kinetic model, to tackle this problem.

We have been particularly focusing on ATP synthase that produces most of ATP required for living activities. The ATP synthase is composed of two rotary motors, Fo and F1. The F1 motor (F1-ATPase) use ATP hydrolysis energy to rotate the central stalk in one direction. By using atomistic molecular dynamics simulations, we clarified timing and pathway of Pi release that produces torque1). We also clarified the coupling mechanism of two rotary motors Fo and F1, based on a master-equation model 2).

2018_okazaki.pngMolecular dynamics simulations of F1-ATPase. Torque on central stalk or biasing potential for Pi are applied to speed up functional dynamics.

Selected Publications

  1. M. I. Mahmood, H. Noguchi and K. Okazaki “Curvature induction and sensing of the F-BAR protein Pacsin1 on lipid membranes via molecular dynamics simulations”, Scientific Reports 9, 14557, doi: 10.1038/s41598-019-51202-z (2019)
  2. K. Okazaki, D. Wöhlert, J. Warnau, H. Jung, Ö. Yildiz, W. Kühlbrandt and G. Hummer “Mechanism of the electroneutral sodium/proton antiporter PaNhaP from transition-path shooting”, Nature Communications 10, 1742, doi:10.1038/s41467-019-09739-0 (2019)
  3. A. Nakamura, K. Okazaki, T. Furuta, M. Sakurai and R. Iino, “Processive chitinase is Brownian monorail operated by fast catalysis after peeling rail from crystalline chitin.” Nature Commun. 9, 3814, doi:10.1038/s41467-018-06362-3 (2018).
  4. 岡崎圭一 “F1-ATPaseの機能的運動のマルチスケールな解析:リン酸解離からγサブユニット回転の弾性・摩擦まで.” 生物物理 55:208-209 (2015).
  5. K. Okazaki & G. Hummer, “Elasticity, friction, and pathway of gamma-subunit rotation in FoF1-ATP synthase.” Proc. Natl. Acad. Sci. U S A 112:10720-10725 (2015).
  6. K. Okazaki & G. Hummer, “Phosphate release coupled to rotary motion of F1-ATPase.” Proc. Natl. Acad. Sci. U S A 110:16468-16473 (2013).