BME 281 Presentation 2 – Ron Greene
“The few wonders of the world only exist while there are those with the sight to see them.” –
Charles de Lint ( Celtic folk musician )
1609 - Galileo Galilei develops compound microscope
1951 - Erwin Müller invents field ion microscope; sees first atoms
1964 - Aaron Klug shows Xray diffraction could be used to develop crystallographic electron microscopy
1971 - Protein Data Bank established as a repository for 3D structural data of proteins and nucleic acids
1978 - Kurth Würthrich used NMR to determine protein structures
1981 - Don Wiley determined the structure of the hemagglutinin protein from the surface of the influenza virus
1998 - Rod MacKinnon publishes first high-resolution structure of an ion channel
2007 - Brian Kobilka solves first structure of a human G protein coupled receptor
Crystallized proteins 4π – FGP stained live yeast
4pi – laser scanning flourescence microscope ~ 100nm scale
Xray crystallography – destroys subject material, no dynamic information
Nuclear Magnetic Resonance microscopy –capable of 1-2 Å resolution. Capable of imaging dynamic processes in vivo .
H1receptor – Xray and NMR
Spin – fundamental physical property of protons, electrons and neutrons
Nuclear Magnetic Resonance – a phenomenon which occurs in certain atoms when exposed to magnetic field
Elements with enough net spin resonate with detectable magnitudes
When placed in a magnetic field of strength B, a particle with a net spin can absorb a photon, of frequency ω.
Chemical shift affects the Larmor frequency at which a given atom resonates
Chemical shift is a precise metric of the chemical environment of an atom
After hitting with pulse to elevate energy states, NMR is measured by induction as nuclei relax to lower state
HOW TO REACT WHEN YOUR NMR IS SENDING MIXED SIGNALS
NMR signal contains many components, each with its own Larmor frequency
This signal, called Free
(FID) decays with time
Fourier analysis is used to transform the signal from time domain to frequency domain.
“Here’s the plan: We put the band back together, do some gigs, earn some bread, bang!” – Jake Blues
The Protein Data Bank continues to expand, including more proteins in more of their naturally occurring conformations
NMR microscopy and clinical
MRI merge to offer real time imaging of biological processes on an atomic scale
 URI BME 281 BME Seminar II <www.ele.uri.edu/courses/bme281>.
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 Oleg Yu Federoff, Miguel Salazar, Haiyong Han, Violetta Chemeris, Sean Kerwin, Laurence Hurley. "NMR-Based Model of a
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 Seui Ogawa, david Tank, Ravi Menon, Juitta Ellerman, Seong-Gi Kim, Hellmut Merkle, Kamil Ugurbil. "Intrinsic signal changes accompanying sensory stiimulation: Functional brain mapping with magnetic resonabce imaging." Proceedings of the National
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