• Oct 26, 2017 (15:00~16:30)

    "Allosteric activation of membrane-bound glutamate receptors using coordination chemistry within living cells"

    Prof. Shigeki Kiyonaka, Prof. Itaru Hamachi (Kyoto University)

    The controlled activation of proteins in living cells is an important goal in protein-design research, but to introduce an artificial activation switch into membrane proteins through rational design is a significant challenge because of the structural and functional complexity of such proteins. Here we report the allosteric activation of two types of membrane-bound neurotransmitter receptors, the ion-channel type and the G-protein-coupled glutamate receptors, using coordination chemistry in living cells. The high programmability of coordination chemistry enabled two His mutations, which act as an artificial allosteric site, to be semirationally incorporated in the vicinity of the ligand-binding pockets. Binding of Pd(2,2′-bipyridine) at the allosteric site enabled the active conformations of the glutamate receptors to be stabilized. Using this approach, we were able to activate selectively a mutant glutamate receptor in live neurons, which initiated a subsequent signal-transduction pathway.(Ref. Nat. Chem., 8, 958–967 (2016).)

  • Dec 8, 2015 (10:30~12:00)

    "Eeffects of confinement on models of intracellular macromolecular dynamics"

    Prof. Edmond Chow (Georgia Institute of Technology)

    The motions of particles in a viscous fluid confined within a spherical cell have been simulated using Brownian and Stokesian dynamics simulations. High volume fractions mimicking the crowded interior of biological cells were used. Importantly, although confinement yields an overall slowdown in motion, the qualitative effects of motion in the interior of the cell can be effectively modeled as if the system were an infinite periodic system. However, we observe layering of particles at the cell wall due to steric interactions in the confined space. Motions of nearby particles are also strongly correlated at the cell wall, and these correlations increase when hydrodynamic interactions are modeled. Further, particles near the cell wall have a tendency to remain near the cell wall. A consequence of these effects is that the mean contact time between particles is longer at the cell wall than in the interior of the cell. These findings identify a specific way that confinement affects the interactions between particles and points to a previously unidentified mechanism that may play a role in signal transduction and other processes near the membrane of biological cells.(Ref. Proc. Natl. Acad. Sci. USA, 112, 14846–14851 (2015).)

  • January 9, 2014 (10:30~13:00)

    "Can the protein structure explain the biological function -a case study in kinesin-microtubule system"

    Dr. Yasushi Okada (RIKEN QBiC)

  • January 8, 2014 (10:00~12:00)

    "Recent research on lipid raft"

    Prof. Akihiro Kusumi (Institute for Frontier Medical Sciences, Kyoto University)

  • September 5, 2013 (10:30~12:00)

    "Peptide Chemistry Based Structural Biology for Receptor Tyrosine Kinase"

    Dr. Takeshi Sato (Institute for Protein Research, Osaka University)

  • May 31, 2012 (13:00~15:00)

    " "In situ" protein structure and dynamics observation by NMR"

    Dr. Kohsuke Inomata (RIKEN Quantitative Biology Center)

    In-cell NMRとは細胞内蛋白質に対する選択的な高分解能異種核多次元NMR測定のことで、蛋白質の構造・動的挙動を原子レベルで解析することが可能である。我々は、HIV-1ウイルスのTat1蛋白質由来のCell Penetrating Peptide(CPP)を利用して、高効率に安定同位体標識された蛋白質を細胞質に導入することで、ヒト等高等哺乳動物体細胞におけるin-cell NMR測定に成功した。またその過程で、pyrenebutyrateによる細胞処理、細胞質におけるCPPの切断が、目的蛋白質の細胞質・核質への均一な導入に必須であることを見出した。更に、上記手法を用いて、細胞内における蛋白質の、細胞内在性の蛋白質との相互作用と、外部投与した低分子薬剤との相互作用を検出する試みを行い、一定の成果を得た。また、細胞内での蛋白質の構造安定性を重水素/軽水素交換実験によって解析したところ、in vitroに比べて不安定であることを示唆する結果を得た。上記に示すように、in-cell NMRという手法を用いることによって、高等哺乳動物体細胞内のような複雑な環境下において、特定の蛋白質の構造・動態を原子レベルで解析することが可能となった。本発表では、これまでの成果を概観するとともに、現在進行中のプロジェクト、特に細胞内蛋白質の構造安定性解析に関する進捗と今後の展望について述べる。

  • April 5, 2012 (13:00~15:00)

    "Free energy analysis of solvent effect on biomolecules using the method of energy representation"

    Dr. Yasuhito Karino (Institute for Chemical Research, Kyoto University)

    Solvation free energy is one of the most important physical quantities to elucidate the hydration effect on protein in solution phase. In this study, the solvation free energy of horse heart cytochrome c immersed in water was calculated using the molecular dynamics simulation coupled with the energy-representation method. The protein intramolecular energy and the solvation free energy are found to compensate each other in the course of equilibrium structural fluctuation, and the roles of the attractive and repulsive components in the protein-water interaction are examined for the solvation free energy.

  • October 3, 2011 (13:30~15:00)

    "Studies of Soft Condensed Matter Systems Using Molecular Simulations: Recent Developments in Non-Additive Electrostatic Potentials and Applications"

    Prof. Sandeep Patel (Department of Chemistry and Biochemistry, University of Delaware, USA)

    Molecular simulations today are applied across many scientific disciplines. Complementing experiment, these tools afford a molecular-level understanding and interpretation of physico-chemical processes at spatial and temporal resolutions inaccessible to experiment. At the heart of such methods is the description of interactions between atoms and molecules, the force field. Traditionally, non-reactive force fields have treated electrostatic interactions using an additive, Coulomb model between fixed partial charges on atomic sites. Though quite successful, there has been conjecture as to the effects of incorporating non-additivity in classical force fields, particularly in biological systems. Over the last several decades, attempts to incorporate electrostatic non-additivity in the form of inducible dipole interactions or dynamically varying partial charges have provided a vast body of knowledge that has aided in the development of a new class of force fields attempting to explicitly account for non-additive effects. We will present our recent work in developing one such class of models, charge equilibration force fields, and select applications of such models to aqueous solution interfaces, ion solvation and specific ion effects, hydrophobocity, model membrane bilayers and simple integral membrane peptides such as the gramicidin A bacterial channel, and protein-ligand binding. Finally, we will discuss recent development and application of graphical processing units (GPU's) for molecular dynamics simulations.

  • September 20, 2011 (13:30~15:00)

    "Membrane Protein Functional Dynamics"

    Dr. Morten O. Jensen (D.E.Shaw Research, New York, USA)

    Long molecular dynamics (MD) simulations, which recently reached the millisecond timescale for the first time, may prove a powerful tool in advancing the understanding of protein function. Here I will discuss our MD studies of the conformational changes associated with ion channel voltage gating. Our results reveal an atomic-level structural mechanism applicable to the entire Na+/K+/Ca2+ voltage-gated ion channel superfamily, reconciling much apparently conflicting experimental data.

  • September 2, 2011 (10:00~15:00)


    Dr. Kiyoshi Yagi (University of Illinois at Urbana-Champaign, USA)


  • August 4, 2011 (13:30~15:00)

    "Spontaneous Binding and Insertion of Membrane-Anchoring Proteins Captured by a Novel Membrane-Mimetic System"

    Dr. Zenmei Ohkubo (Department of Biochemistry and Beckman Institute, University of Illinois at Urbana-Champaign, USA)

    Characterizing atomic details of membrane binding of peripheral membrane proteins by molecular dynamics (MD) has been seriously hindered by the slow dynamics of membrane reorganization associated with the phenomena. Consequently, the resulting structures are largely biased by the initial configuration of the lipids and proteins in the simulation system. To expedite lateral diffusion of lipid molecules and to accelerate formation of the optimal interaction between peripheral proteins and lipid headgroups during MD simulations, we have developed a highly mobile membrane mimetic (HMMM) model. The HMMM model is composed of an organic solvent layer as the hydrophobic core sandwiched by water and with short-tailed phospholipids at the interface whose acyl tails are immersed in the organic phase. This configuration is formed spontaneously and rapidly, regardless of the initial position or orientation of the short-tailed lipids. The short-tailed lipids in the HMMM model exhibit about two orders of magnitude larger lateral diffusion than full lipids in conventional membrane models, whereas the membrane profile of the HMMM model is essentially the same as those of the full-membrane models. As a challenging test of membrane binding of a peripheral protein without any guide, the GLA domain of human coagulation factor FVII was initially placed in bulk water in the HMMM model to simulate. During the MD simulation, the GLA domain inserted itself into the membrane spontaneously and reproducibly, with interactions closely matching those obtained previously using full membranes. The HMMM model is extremely efficient in capturing the mechanism of membrane binding of a wide spectrum of peripheral proteins, as well as other membrane-associated phenomena.

  • June 9, 2011 (13:30~15:00)

    "Binding and Folding of Intrinsically Disordered Proteins: Nascent Structures vs Intrinsic Flexibility"

    Prof. Jinahan Chen (Department of Biochemistry, Kansas State University, USA)

    Intrinsically disordered proteins (IDPs) are a class of newly recognized functional proteins that rely on a lack of stable structure for function. They are highly prevalent in biology, play key roles in crucial cellular functions, and are extensively involved human diseases. For signaling and regulation, IDPs frequently fold into stable structures upon recognition of specific targets. Understanding the mechanisms of these binding-folding interactions is of significant importance because they underlie the organization of important regulatory networks that control various aspects of cellular decision-making. I will discuss some of the key lessons that we have learned from our recent atomistic and coarse-grained simulations several small regulatory IDPs. In particular, I will discuss how an intriguing interplay of nascent structures, intrinsic flexibility, and charges might facilitate efficient and versatile regulation of IDP function.


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