mechanisms of information transfer across biological …rnc.rpi.edu/2014symposium/neale, christopher...
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Mechanisms of Information Transfer across Biological Membranes: G protein-Coupled Receptors
Chris Neale
Postdoc
Department of Physics, Applied Physics, and Astronomy
Rensselaer Polytechnic Institute, Troy, NY, USARensselaer Polytechnic Institute, Troy, NY, USA
2014 Rensselaer Nanotechnology Center Research SymposiumWednesday, October 29, 2014
Advisor: Angel E. García
Collaborators: Régis Pomès, University of Toronto, Canada
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Creative Commons (Asd.and.Rizzo)
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Creative Commons (Mariana Ruiz)
Cell membranes
M.W. Brightman and T.S. Reese. J. Cell. Biol. 1969. 40(3):648-77
x34,000
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Membrane proteins
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GPCRs are excellent drug targets
Information
InformationA.L. Hopkins, C.R. Groom. Nat. Rev. Drug Discov. 2002. 1(9):727-730
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GPCR activation
PDB: 3SN6; Rasmussen et al. Nature. 2011. 477:549-555
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An “ionic lock” stabilizes inactive conformations
inactiveactive inactiveactive
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Molecular dynamics simulations
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Spontaneous formation of the ionic lock
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The cytosolic binding pocket is more stable in apo-state simulations using a crystal structure containing a G protein than a mimetic nanobody
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The ionic lock forms less frequently in apo-state simulations using a crystal structure containing a G protein than a mimetic nanobody
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What is the molecular source of this differential active-state stability?
Future work
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Supervisor:Dr. Angel García
Group Members:Anthony BishopCalvin ChenDr. Charles EnglishDr. Henry HerceJoel JankeRyan KrafnickBryan MakowskiTyler MasonJacob MinerDavid RosenmanJorge OchoaJorge Ochoa
Recent Alumni:Dr. Alan ChenDr. Camilo Jimenez-CruzDr. Kun HuangDr. Akansha Saxena
MCB-1050966