Multi-wavelength anomalous diffraction

Multi-wavelength anomalous diffraction (sometimes Multi-wavelength anomalous dispersion; abbreviated MAD) is a technique used in X-ray crystallography that facilitates the determination of the three-dimensional structure of biological macromolecules (e.g. DNA, drug receptors) via solution of the phase problem.^[1]

MAD was developed by Wayne Hendrickson while working as a postdoctoral researcher under Jerome Karle at the United States Naval Research Laboratory.^[2] The mathematics upon which MAD (and progenitor Single-wavelength anomalous diffraction) was based were developed by Jerome Karle, work for which he was awarded the 1985 Nobel Prize in Chemistry (along with Herbert Hauptman).

Compared to the predecessor SAD, MAD has greatly elevated phasing power from using multiple wavelengths close to the edge. However, because it requires a synchrotron beamline, a longer exposure (risking radiation damage), and only allows a limited choice of heavy atoms (those with edges reachable by a synchrotron), MAD has declined in popularity relative to SAD.^[3]

References

^ Hendrickson W, Ogata C (1997). Phase determination from multiwavelength anomalous diffraction measurements. Methods in Enzymology. Vol. 276. pp. 494–523. doi:10.1016/S0076-6879(97)76074-9. ISBN 978-0-12-182177-7. PMID 27799111.
^ Hendrickson WA (1985). "Analysis of Protein Structure from Diffraction Measurement at Multiple Wavelengths". Transactions of the ACA. 21.
^ "Dictionary of common terms used in PHENIX". phenix-online.org. MAD: [...] The differences in anomalous scattering around the edge allow calculation of phase angles without the phase ambiguity present in SAD experiments, although density modification will usually still be necessary to obtain an easily interpretable map. [...] Although very powerful, MAD phasing has declined somewhat in popularity relative to SAD because of the more limited choice of heavy atoms, the difficulty of avoiding radiation damage, and the requirement for a synchrotron beamline.

External links

MAD phasing — an in depth tutorial with examples, illustrations, and references.
HHMI Bio for Wayne Hendrickson
Wayne Hendrickson Home Page
Hendrickson Laboratory Summary of Research
Jerome Karl Nobel Biography
NRL Recognition of Nobel Prize

Computer programs

The SSRL Absorption Package — Brennan S, Cowan PL (1992). "A suite of programs for calculating x-ray absorption, reflection and diffraction performance for a variety of materials at arbitrary wavelengths". Review of Scientific Instruments. 63 (1): 850. Bibcode:1992RScI...63..850B. doi:10.1063/1.1142625.
CHOOCH — Evans G, Pettifer RF (2001). "CHOOCH: a program for deriving anomalous-scattering factors from X-ray fluorescence spectra". Journal of Applied Crystallography. 34: 82–86. doi:10.1107/S0021889800014655.
Shake-and-Bake (SnB) — Smith GD, Nagar B, Rini JM, Hauptman HA, Blessing RH (1998). "The use of Snb to determine an anomalous scattering substructure". Acta Crystallographica D. 54 (Pt 5): 799–804. doi:10.1107/S0907444997018805. PMID 9757093.
SHELX — Sheldrick GM (1998). "SHELX: applications to macromolecules". In S Fortier (ed.). Direct methods for solving macromolecular structures. Dordrecht: Kluwer Academic Publishers. pp. 401–411. ISBN 0-7923-4949-0.