3D biochemical Modeling Using Nuclear Magnetic Resonance Microscopy

1
3D biochemical Modeling Using Nuclear Magnetic
Resonance Microscopy
BME 281 Presentation 2 Ron Greene
2
The importance of visualization
The few wonders of the world only exist while
there are those with the sight to see them.
Charles de Lint (Celtic folk musician )
3
A Brief History of 3D Molecular Modeling
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

4
Techniques for Molecular Imaging
4p FGP stained live yeast
Crystallized proteins

• 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
5
What is nuclear magnetic resonance?

• 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

6
How does One Make a Nucleus resonate?
When placed in a magnetic field of strength B, a
particle with a net spin can absorb a photon, of
frequency ?.
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
Chemical shift
After hitting with pulse to elevate energy
states, NMR is measured by induction as nuclei
relax to lower state
Larmor frequency
Gyroscopic ratio
7
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 Induction Delay (FID)
decays with time
Fourier analysis is used to transform the signal
from time domain to frequency domain.
8
Heres the plan We put the band back together,
do some gigs, earn some bread, bang! Jake Blues
9
To infinity and beyond
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
10
Magnet therapy works, man
References 1 URI BME 281 BME Seminar II
ltwww.ele.uri.edu/courses/bme281gt. 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 lthttp//en.wikipedia.org/wiki/Nuclea
r_magnetic_resonanceNMR_spectroscopygt.