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Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Simulations of Biomolecules in Cellular Crowded Environments

The inside of cell is highly crowded with proteins, nucleic acids, ribosomes, metabolites, and so on. The high concentration of proteins realizes macromolecular crowding environments, which can affect protein behaviors in cells. The effect of macromolecular crowding was mainly interpreted via the excluded volume effect, which favors the compact and globular structures of proteins in the crowded environment. However, recent in-cell NMR spectroscopy and atomistic molecular dynamics (MD) simulations in explicit solvent (R. Harada eta al. JACS (2012, 2013)) have shown the importance of weak protein-protein interactions on protein stability and dynamics. In the talk, we discuss the effect of macromolecular crowding on protein-metabolite or protein-ligand interactions. In the simulations of the all-atom model of Mycoplasma Genitalium (I. Yu et al. eLife (2016)), we observed that not only hydrophobic but also hydrophilic metabolites also stay on the surfaces of proteins longer than in the bulk solution. Non-specific and weak protein-metabolite interaction is likely important for the metabolite distributions. We also investigated kinase-inhibitor binding processes in dilute solution and protein crowded environment by all-atom MD simulations and observed different binding processes in those two conditions.

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Figure 1. All-atom MD simulation of the cytoplasm of Mycoplasma Genitalium (This figure is taken from I. Yu et al. eLife (2016)).

References

    R. Harada, Y. Sugita, & Feig, M. (2012). Protein crowding affects hydration structure and dynamics, J. Am. Chem. Soc. 134, 4842-4849.

    R. Harada, N. Tochio, T. Kigawa, Y. Sugita, & Feig, M. (2013). Reduced Native State Stability in Crowded Cellular Environment Due to Protein-Protein Interactions”, J. Am. Chem. Soc.. 134, 3696-3701.

    I. Yu, T. Mori, T. Ando, R. Harada, J. Jung, Y. Sugita, M. Feig, “Biomolecular interactions modulate macromolecular structure and dynamics in atomistic model of a bacterial cytoplasm”, eLife 5, e19274, 2016.

Yuji Sugita1,2,3,*
Kento Kasahara2
Hiraku Oshima2
Isseki Yu4
Grzegorz Nawrocki5
Suyong Re1
Michael Feig 2.5

1RIKEN Center for Pioneering Research
2RIKEN Center for Biosystems Dynamics Research
3RIKEN Center for Computational Science
4Maebashi Institute of Technology
5Michigan State University
2-1 Hirosawa, Wako-shi
Saitama, Japan, 351-0198*

Ph: 81 (48) 462-1407
Fx: 81 (48) 467-4532
Email: sugita@riken.jp *