金沢大学 ナノ生命科学研究所

Prof. Alexander S. Mikhailov

Simple computational models for exploring complex bio-dynamic phenomena

Computational molecular biophysics is a powerful approach for simulating the dynamics of complex biological structures ranging from single molecules to the cell

Alexander Mikhailov, Professor, Nano Life Sciences Institute (WPI-NanoLSI), Kanazawa University

“I am a theoretical physicist but consider myself more of an applied mathematician, and I develop models to analyze and describe experimental results,” says Mikhailov. “I currently have 10,000 citations on topics ranging from social systems to inorganic physical chemistry and molecular biophysics. Of course, I am not an expert in all these fields, but I have worked with people who are experts.”

Mikhailov graduated from a high school in Moscow that excelled in teaching mathematics. He decided to enrol at University of Moscow and study theoretical physics inspired by Nobel Laureate Lev Landau, who was still teaching there. “I published my first scientific paper when I was 23 and still an undergraduate. My PhD was on non-equilibrium condensed matter and later I moved to chemical and biological complex systems.”

COVID-19 and research in Germany
Mikhailov says that restrictions in Germany and Europe due to the spread of COVID-19 are much stronger than in Japan with restaurants and theatres closed and limitations on outdoor activities. “The Fritz Haber Institute, where I also work, was closed for a while but now we can use its facilities by following new guidelines to prevent the spread of COVID-19. Now, research continues, and experiments go on. People often work from home using the internet to stay in touch.”

Research at the NanoLSI
Mikhailov is collaborating with his colleagues at the NanoLSI on modelling molecular motors, such as the motor-protein myosin. “Normally the operation of a motor needs fuel,” explains Mikhailov. “The chemical fuel for myosin is ATP but researchers at Kanazawa have developed interactive atomic force microscopy that enables the application of perturbations at precise timings to single molecules. Using this approach, they induced translational motion or walking of single myosin molecules over actin filaments on surfaces. So the driving energy is not chemical but mechanical in this case. We developed a model to explain these results and reported it at the Annual Meeting of the Biophysical Society of Japan in September 2019.”

Plans for the future
Mikhailov wants to focus more on modelling systems on the cellular level because the researchers at the NanoLSI have a wide range of expertise in areas including cancer research and life sciences. “As a theoretician I want to model at the cellular level, as well as continuing biophysics of single molecules,” says Mikhailov. “We are also thinking about post-COVID and consider having a conference in Berlin where scientists from the NanoLSI can present their research and discuss it with German colleagues. I have already booked the conference hall in Berlin. We can only hope that it will be possible to start international travel again towards the beginning of 2022.”

Research highlights
In their paper entitled, “Simple mechanics of protein machines”, Alexander Mikhailov and Holger Flechsig (a member of Alexander Mikhailov’s group at the NanoLSI) give a comprehensive review on how the behavior of protein machines can be understood using “simple mechanical models of elastic networks” [1].

In an excellent book covering complex self-organization processes in molecular systems, Alexander Mikhailov and Nobel Laureate Gerhard Ertl offer “an outline of underlying theoretical concepts and their experimental verification, as they emerged in the middle of the twentieth century and evolved afterwards.” [2].

In a recent preprint, Mikhailov and his colleagues describe the “Quantification and demonstration of the collective constriction-by-ratchet mechanism in the dynamin molecular motor.” Their integrated approach combining both experimental and computational modeling has allowed them to decipher the operation of dynamin and to show how the collective motor behavior in megadalton molecular assemblies can be computationally reproduced [3].

References
[1] H. Flechsig and A. S. Mikhailov, Simple mechanics of protein machines. J. R. Soc. Interface 16: 20190244, (2019).
http://dx.doi.org/10.1098/rsif.2019.0244

[2] A.S. Mikhailov and G. Ertl, Chemical Complexity: Self-Organization Processes in Molecular Systems, Springer, 2017.
ISBN 978-3-319-57377-9
https://www.springer.com/gp/book/9783319573755

[3] O. Ganichkin et al, Quantification and demonstration of the collective constriction-by-ratchet mechanism in the dynamin molecular motor, O. Ganichkin et al, bioRxiv preprint https://doi.org/10.1101/2020.09.10.289546

 

Further information
NanoLSI Podcasts
This episode offers greater insights into Professor Alexander Mikhailov’s research at the NanoLSI.

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NanoLSI Podcast

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