Current Research at NanoLSI

Our research is closely related to the experiments undertaken in the Nano Life Science Institute. We aim to provide theoretical support to the investigations of bio-dynamics at nanoscales. This includes analysis and interpretation of the obtained results, but also proposing ideas for new experiments that might be performed. Moreover, we study selected fundamental theoretical problems in molecular biophysics of the cells. The emphasis in our research is on developing and exploring relatively simple models of complex biophysical phenomena which are nonetheless capable to reproduce the principal phenomena involved. To a large extent, our studies are carried together with the experimental groups in NanoLSI, as well as in collaborations with scientists from other research centers in Japan and abroad.

Biological nano-systems of a cell are approached in our investigations at three structural levels: single macromolecules (enzymes, molecular motors and protein machines), mesoscopic aggregates (filaments and membranes), and collective multiparticle phenomena in living biological cells.

Single macromolecules - protein machines and motors

Multi-scale models are employed to study functional conformational dynamics of proteins in simulations. Often coarse-grained descriptions, but also phenomenological models, are considered to explain observations from high-speed AFM experiments of biological machines.

• Myosin V motor dynamics
  In a collaboration project with the group of Toshio Ando we aim to explain results from high-speed AFM experiments, in which walking of the myosin V motor along actin filaments can be visualized.
  

• ABC transporter cycles
  We use coarse-grained structure-based models to study conformational motions underlying entire ATP-dependent operation cycles in membrane ABC transporters. We provide explanation of high-speed AFM experiments for such transporters performed at NanoLSI.

Mesoscopic aggregates

We use multi-scale descriptions are used to study interactions between proteins and filamentous large-scale assemblies. The aim of our current theoretical project (together with MDC and the Free University of Berlin) is to undertake multi-scale mathematical modeling and computer simulations of dynamin filaments on deformable membrane tubes.

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• Dynamin filament dynamics
  Dynamin combines features of a molecular motor and a structural protein. It builds filaments that coil around membrane tubes and, under GTP hydrolysis, performs scission of the tubes.











• Multi-scale simulations
  Computer simulations reveal that, even in absence of GTP, dynamin can constrict (but without scission) membrane tubes and, moreover, interactions with the membrane affect the filament shape. For details, see J. Noel, Biophys. J. (2019). In the future, the effects of motor operation in this model are planned to be theoretically explored.

Collective phenomena in cells

The cytoplasm of bacterial cells represents a crowded solution of proteins that operate as enzymes, molecular motors and other protein machines. Within a living cell, most of such proteins would change their conformation in each operation or turnover cycle. Possible general mechanisms of metabolism-induced fluidization of the cytoplasm, seen in experiments, are theoretically investigated by us in a joint project with researchers from the Chiba and Tohoku universities in Japan.

• Crowded colloids of active proteins
  Multi-particle computer simulations of a non-equilibrium model colloid that consists of particles cyclically changing their shapes are performed. See the preprint (https://arxiv.org/abs/1909.03949).

Movies from previous research

Modeling operation cycles of molecular motors

Tracing entire operation cycles of molecular motor hepatitis C virus helicase in structurally resolved dynamical simulations. Proc Natl Acad Sci USA 107, 20875-20880 (2010)

Molecular Movies of F1-ATPase motor

In a collaboration project with Jin Yu, multi-scale simulations of the F1-ATPase ring motor were performed. The intrinsic inter-domain couplings underlying the rotating pattern of catalytic activity in the ring could be identified, and a model of motor coordination in the absence of the central motor was provided. See Biophys J 113, 558-571 (2017)

Evolutionary design of protein-like structures

Examples of designed elastic networks which mimic the operation of protein machines.
Designed machine in a biological membrane. J Chem Phys 138, 195101 (2013)
Constructed model protein motor. New J Phys 18, 043006 (2016)
Designed allosteric structures. Biophys J 113, 558-571 (2017)