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.

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 )

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

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

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.

4π – FGP stained live yeast

H1receptor – Xray and NMR

Crystallized proteins

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

Gyroscopic ratio Larmor frequency

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

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

NMR signal contains many components, each with its own Larmor frequency

This signal, called Free Induction Delay (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 Future:

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

REFERENCES[1] URI BME 281 BME Seminar II <www.ele.uri.edu/courses/bme281>.[2] J Puerta-Fonolla, T Vasquez-Osorio, J ruiz-Cabello, J Murillo-Gonzalez, A Pena-Melian. "Margentic resonance microscopy versus light microscopy in embryology teaching." Clinical Anatomy (2004): 429-435.[3] Oleg Yu Federoff, Miguel Salazar, Haiyong Han, Violetta Chemeris, Sean Kerwin, Laurence Hurley. "NMR-Based Model of a Telomerase-Inhibiting Compound Bound to G-quadruplex DNA." Biochemistry (1998): 12367-12374.[4] 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 Academy of Science (1992): 5951-5955.[5] wiki. "Nuclear magnetic Resonance." 22 October 2011. Wikipedia. 5 November 2011 <http://en.wikipedia.org/wiki/Nuclear_magnetic_resonance#NMR_spectroscopy>.