3SBA-04 Prospects on artificial molecular motor by redesigning of F1-ATPase(Rise of molecular machines,Symposium,The 52th Annual Meeting of the Biophysical Society of Japan(BSJ2014))
3SBA-04 F1 モーターの再デザインによる人工回転分子モーター開発の見通し(分子機械デザイン,シンポジウム,第52回日本生物物理学会年会(2014年度))

Hiroyuki Noji
2014 Seibutsu Butsuri  
I'll discuss the application of molecular simulations to proton pumps and biomolecular motors. The applications highlight that calibrated QM/MM methods are valuable because they provide not only energetic/kinetic information for the relevant chemical driving force (e.g., ATP hydrolysis) but also spectroscopic observables that can be compared to experiments. A feature emerged from these studies is that changing hydration level of protein cavities may play an important role in modulating the
more » ... ivity of key groups and thus the timing of chemical events. Thus, connections between conformational transitions, hydration changes and chemical activities form the basis of "mechanochemical coupling" in biomolecular machines. 3SBA-04 F1 モーターの再デザインによる人工回転分子モーター開発 の見通し Prospects on artificial molecular motor by redesigning of F1- ATPase Hiroyuki Noji (Applied Chem. U-Tokyo) F1-ATPase, soluble and catalytic domain of ATP synthase is the rotary motor protein in which the catalytic stator ring rotates the inner rotary shaft upon ATP hydrolysis. Chemomechanical coupling mechanism of F1 has been well studied and F1 became one of the best-characterized molecular motors. Recent studies revealed that the rotation mechanism of F1 is unexpectedly robust against global mutagenic perturbations. Thus, the basis has been set for the rational or semi-rational designing of F1. Such a synthetic approach will test the working hypotheses and give important insights on the design principle of F1. After reviewing on recent studies on the design principle of F1, I will introduce the current status of ongoing F1 design project. 3SBA-05 Is enzyme evolution reversible? Exploring fitness landscapes by laboratory evolution Nobuhiko Tokuriki (University of British Columbia) The extent to which mutations interact each other or epistasis dictates how protein evolves to new functions. Although importance of epistasis has been well recognized in protein as well as organismal evolution, molecular basis underpinning epistasis is poorly studied. Here I present experimental evolution to explore fitness landscape. I discuss our findings of highly restricted the fitness landscape of phosphotriesterase (PTE) activity by performing laboratory evolution between PTE and arylesterase. I present molecular constraints underlying extensive epistasis between mutations, leading genetic irreversibility and incompatibility. Our findings indicate that understanding constraints in evolution will help us to understand and predict protein evolution and design. 3SBA-06 Remote control of myosin and kinesin motors using lightactivated gearshifting Zev Bryant (Stanford University) Engineering biomolecular motors provides direct tests of structure-function relationships and potential tools for controlling cellular processes or harnessing molecular transport. I will describe the creation of a panel of cytoskeletal motors that reversibly change gears -speed up, slow down, or switch directions -when exposed to blue light. Our genetically encoded structural designs incorporate a photoactive protein domain to enable light-dependent conformational changes in an engineered lever arm. Using in vitro motility assays, we have confirmed robust spatiotemporal control over motor function and characterized the kinetics of optical gearshifting. Our modular approach has yielded controllable motors for both actin-based and microtubule-based transport. 3SCA-01 生物システムの理解に本質的な3つの未解決問題 Three unsolved problems for essential understanding of biological systems Shigeki Mitaku (Toyota Phys. Chem. Res. Inst.) I discuss the relationship among three certain unsolved problems for understanding biological systems: (1) Is there any simple principle of the protein structure formation? (2) How an enormously large number of cellular processes are harmonized in biological systems? (3) How the integration of many random mutations can design the robustness of living things? Such problem seems unsolvable, if we do not take the close relationship among the three problems into account. However, suppose that any cellular system for regulating mutations has been developed in the evolutionary process, we will have an obvious solution of all the problems. I will show several evidences for the relationship among the unsolved problems and discuss on the future direction of the bioinformatics. Cellular responses are composed of dynamic molecular interactions between multiple layers including protein phosphorylation, and metabolites. To reveal an unbiased whole picture, simultaneous quantitative and global measurements in these layers, rather than pin-point analysis of some selected molecules, is needed. Here, we simultaneously performed metabolomic and phospho-proteomic analysis in insulinstimulated Fao hepatoma cells in collaboration with Prof. Soga (Keio Univ), and Dr. Matsumoto and Prof. Nakayama (Kyushu Univ), respectively, and developed an reconstruction method of insulin-dependent metabolic control pathway directly from trans-OMICS data. In this symposium, reconstruction of global molecular network directly from trans-OMICS data is discussed. -S137 -Symposium
doi:10.2142/biophys.54.s137_2 fatcat:6zcoeghf7va37dcfkte22zrei4