How do we determine the structures of biological molecules?

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How do we determine the structures of biological
molecules?
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Mineral Crystals
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Two-Dimensional CrystalTranslational Symmetry
M.C. Escher
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Crystal Lattice
Alexander McPherson, Introduction to
Macromolecular Crystallography Wiley-Liss, 2002
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Two-Dimensional Crystal With Mirror Symmetry
M.C. Escher
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Crystal Systems
Jenny Pickworth Glusker, Kenneth N. Trueblood,
Crystal Structure Analysis A Primer, Oxford
University Press, 1985
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Light Diffraction
Henry S. Lipson Crystals and X-rays Taylor
Francis 1970
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X-ray Diffraction
Gale Rhodes, Crystallography Made Crystal Clear
A Guide for Users of Macromolecular Models,
Academic Press, 1993
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X-ray Crystallography
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X-ray DiffractionPhotograph
Rosalind Franklins diffraction photo of DNA
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Electron Density Maps
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CrystalStructures
Hemoglobin
Myoglobin
Lysozyme
Ribonuclease
Myoglobin Kendrew, Bodo, Dintzis, Parrish,
Wyckoff, Phillips, Nature 181 662-666,
1958.Hemoglobin Perutz, Proc. R. Soc. A265,
161-187,1962. Lysozyme Blake, Koenig, Mair,
North, Phillips, Sarma, Nature 206 757, 1965.
Ribonuclease Kartha, Bello, Harker, Nature 213,
862-865 1967. Wyckoff, Hardman, Allewell,
Inagami, Johnson, Richards. J. Biol. Chem. 242,
3753-3757, 1967.
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The Steps in the Process

• Isolation,
• Expression,
• Purification,
• Crystallization

Target Selection
Data Collection
Structure Solution
Structure Refinement
Functional Annotation
Publication
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Vapor diffusion
McPherson, A. Crystallization of Biological
Macromolecules. Cold Spring Harbor Laboratory
Press, 1999, p. 179.
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Protein crystals
McPherson, A. Crystallization of Biological
Macromolecules. Cold Spring Harbor Laboratory
Press, 1999, p. 185.
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Crystal mounting
Glusker, J. Trueblood, K. Crystal Structure
Analysis A Primer. Oxford University Press,
1985, p. 44.
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Sealed Tube Diffractometer
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Rotating Anode Diffractometer
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Synchrotron X-ray source
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Synchrotron Beamline Diffractometer
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