2023年3月15日に価値創造研究センター外国人客員教員（長岡研究室受け入れ）Ana-Nicoleta Bondar先生とJohn E. Straub先生による講演会が対面で行われます。ご興味のある方は是非ご参加下さい。
場 所： 情報学研究科棟1F 第1講義室
題 目： Mechanisms by which dynamic water-mediated hydrogen-bond networks shape membrane protein function
講 演 者：Dr. Ana-Nicoleta Bondar
Full Professor, Faculty of Physics, University of Bucharest
Proteins perform reactions fundamental for all biological cells – such as membrane transporters that transport of ions and other solutes across cell membranes, membrane receptors that mediate communication between cells and their environment, or soluble motor proteins that couple an energy-yielding chemical reactions with conformational changes to move cargo. Protein function is intimately related to protein conformational plasticity, for which dynamic hydrogen bonds and hydrogen bond networks are essential. Indeed, hydrogen bond networks and their dynamics are of often central to mechanisms proposed for protein reactions. But description of the dynamic hydrogen-bond networks in proteins and protein complexes is often challenging due to the large numbers of hydrogen bonds, particularly when water-mediated hydrogen bonds must be considered. In the case of protonation-coupled transporters and receptors, an additional challenge is to identify putative proton binding sites and long-distance proton-transfer pathways. To tackle these challenges, we have developed graph-based algorithms and graphical user interfaces that enable efficient computations of dynamic water-mediated hydrogen bond networks in membrane proteins and at lipid membrane interfaces. We apply these algorithms to understand reaction mechanisms of G Protein Coupled Receptors (GPCRs) and protonation-coupled membrane transporters. The lecture will focus on applications of our graph-based algorithms to evaluate dynamical hydrogen-bond networks of large datasets of static structures of GPCRs and membrane transporters, and from atomistic simulations of visual rhodopsins.
題 目： On Computing Equilibrium Binding Constants for Protein–Protein Association in Membranes
講 演 者：Dr. John E. Straub
Full Professor, Department of Chemistry, University of Boston
Protein association in lipid membranes is fundamental to membrane protein function and of great biomedical relevance. All-atom and coarse-grained models have been extensively used to understand the protein–protein interactions in the membrane and to compute equilibrium association constants. We examine the well-studied problem of computing association equilibrium constants for homodimerization of several transmembrane proteins. Conformational sampling is performed using umbrella sampling along previously proposed one-dimensional collective variables and compared with sampling over two-dimensional and three-dimensional collective variable spaces using umbrella sampling and metadynamics. We demonstrate that sampling along one-dimensional collective variables fails to capture thermodynamically important native interactions, while simulations over two-dimensional and three-dimensional collective variable spaces effectively characterizes the thermodynamically relevant native and non-native interactions contributing to the association equilibrium. These results demonstrate the challenges associated with accurately characterizing binding equilibria when multiple poses contribute to the bound state ensemble.