【Cancelled】KGRI Lecture Series: (Mar.10, 2020)"Structure and Dynamics of Biomembranes "2020.03.10
Due to the current spread of infections by Covid-19 (coronavirus disease), we have cancelled the event. We deeply apologize to everyone who intended to participate.
Keio University Global Research Institute (KGRI) aims to promote international research and educational exchange and invites those working in the forefront of research and education in Japan and overseas to give lectures.
On this occasion, Professor Mark S.P. Sansom from University of Oxford in UK will give a lecture titled "Structure and Dynamics of Biomembranes".
Date & time: Tuesday, March 10, 14:30-17:00 (Open 14:00)
Venue: 16th Building-A 3F Meeting Room, Yagami Campus, Keio University
Host: Keio University Global Research Institute's Creativity Initiative
Language: English (No simultaneous interpretation provided)
Other: Open to anyone. No admission fee, Pre-registration not required.
Summary of Lecture:
Part1: Membrane protein interactions with lipids as viewed by molecular simulations.
Interactions with lipids are important in the function of membrane proteins and the organization of membranes. Molecular simulations allow us to explore structural, energetic, and dynamic aspects of these interactions. Coarse-grained (CG) simulations in mixed lipid bilayers allow identification of lipid interaction sites, which may be probed further by estimation of free energy landscapes to explore lipid specificity, and by atomistic simulations to refine models of the structure and dynamics of lipid binding. This approach has been applied to a number of membrane proteins, including transporters, ion channels and receptors. Simulations of lipid interactions with Class A GPCRs has revealed binding sites for cholesterol and PIP2. Interactions with PIP2 have been shown to be dependent on the activation state of the receptor, suggesting a functional role for the lipid via allosteric modulation. Interactions of lipids with other classes of GPCRs have been explored, including of cholesterol and PIP2 with the Class F GPCR Smoothened. Our analysis of the interactions of lipids with ion channels have also focussed on cholesterol and PIP2, both of which are allosteric modulator of a number of ion channel families. PIP2 interactions have been characterised for Kir channels, and more recently for members of the TRP channel family. Simulations of large membrane systems containing multiple copies of Kir channels suggest that the lipid composition of the bilayer can modulate channel-channel interactions within crowded membranes.
Duncan, A., Song, W. & Sansom, M.S.P. (2020) Lipid-dependent regulation of ion channels and GPCRs: insights from structures and simulations. Ann. Rev. Pharmacol. Toxicol.60:31-50.
Part2: Water and Ions in Membrane Nanopores and Channels: Insights from Molecular Simulations.
Molecular dynamics simulations can be used to explore the dynamic behaviour of water within nanopores and biological channels in lipid bilayer membranes. Simulation studies of the behaviour of water in idealised models of nanopores have revealed aspects of the organization and dynamics of nano-confined water, including wetting/de-wetting in narrow hydrophobic nanopores. Simulation studies of nanopores reveal a complex relationship between pore size/geometry, the nature of the pore lining, and rates of water transport. Wider nanopores with hydrophobic linings favour water flow whereas narrower hydrophobic pores may show de-wetting. Simulation studies of the behaviour of water in a range of biological nanopores will be discussed, including β-barrel protein nanopores  and ion channels . Water is shown to play a key role in ion transport in biological channels, and in hydrophobic gating of ion channels. An overall picture emerges whereby the behaviour of water in a nanopore or channel may be predicted as a function of its hydrophobicity and radius . This informs our understanding of the functions of diverse of channel structures and will aid the design of novel nanopores.
 Trick, J.L., Wallace, E.J., Bayley, H., & Sansom, M.S.P. (2014) Designing a hydrophobic barrier within biomimetic nanopores. ACS Nano 8: 11268-11279.
 Trick, J.L., Chelvaniththilan, S., Klesse, G., Aryal, P., Wallace, E.J., Tucker, S.J. & Sansom, M.S.P. (2016) Functional annotation of ion channel structures by molecular simulation. Structure 24: 2207-2216.
 Rao, S., Klesse, G., Stansfeld, P.J., Tucker, S.J., & Sansom, M.S.P. (2019) A heuristic derived from analysis of the ion channel structural proteome permits the rapid identification of hydrophobic gates. PNAS 116: 13989-13995.
Department of Biochemistry, University of Oxford
Faculty of Science and Technology
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