理化学研究所 計算科学研究センター

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第173回 第1部

第173回 第1部
日時: 2019年7月1日(月)、13:00 - 13:55
場所: R-CCS 6階講堂

・講演題目: Molecular Mechanisms for Protein-Ligand Binding in a Living Cell
・講演者: 杉田 有治(粒子系生物物理研究チーム、チームリーダー)
※発表・スライド共に英語

講演要旨:

The inside of cell is highly crowded with proteins, nucleic acids, ribosomes, metabolites, ions and water. In the macromolecular crowding environments, protein behaviors can be altered compared to those in dilute solution. The effect of macromolecular crowding was mainly explained via the excluded volume effect. 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-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 crowded protein solution by all-atom MD simulations.