Multi-wavelength anomalous diffraction explained

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]

See also

• Single wavelength anomalous dispersion (SAD)
• Multiple isomorphous replacement (MIR)
• Anomalous scattering
• Anomalous X-ray scattering
• Patterson map

References

Further reading

• Hendrickson WA . 1985 . Analysis of Protein Structure from Diffraction Measurement at Multiple Wavelengths . Transactions of the ACA . 21.
• Karle J . 2009 . Some developments in anomalous dispersion for the structural investigation of macromolecular systems in biology . International Journal of Quantum Chemistry . 7 . 357–367. 10.1002/qua.560180734.
• Karle J . 1989 . Linear Algebraic Analyses of Structures with One Predominant Type of Anomalous Scatterer . Acta Crystallographica A. 45 . 4 . 303–307. 10.1107/s0108767388013042 . 2559755 . 1989AcCrA..45..303K .
• Pahler A, Smith JL, Hendrickson WA . 1990 . A Probability Representation for Phase Information from Multiwavelength Anomalous Dispersion . Acta Crystallographica A. 46 . 7 . 537–540. 10.1107/s0108767390002379 . 2206480 . 1990AcCrA..46..537P .
• Terwilliger TC . 1994 . MAD Phasing: Bayesian Estimates of FA . Acta Crystallographica D. 50 . Pt 1 . 11–16. 10.1107/s0907444993008224 . 15299471 . free . 1994AcCrD..50...11T .
• Terwilliger TC . 1994 . MAD Phasing: Treatment of Dispersive Differences as Isomorphous Replacement Information . Acta Crystallographica D. 50 . Pt 1 . 17–23. 10.1107/s0907444993008236 . 15299472. free . 1994AcCrD..50...17T .
• Fourme R, Shepard W, Kahn R, l'Hermite G, de La Sierra IL . 1995 . The Multiwavelength Anomalous Solvent Contrast (MASC) Method in Macrocolecular Crystallography . Journal of Synchrotron Radiation. 2 . Pt 1 . 36–48 . 10.1107/S0909049594006680. 16714785 . free . 1995JSynR...2...36F .
• Book: de la Fortelle E, Bricogne G . Maximum-likelihood heavy-atom parameter refinement for multiple isomorphous replacement and multiwavelength anomalous diffraction methods . 1997 . Macromolecular Crystallography Part A . 276 . 472–494 . 10.1016/S0076-6879(97)76073-7 . 27799110 . Methods in Enzymology . 978-0-12-182177-7 . https://archive.org/details/macromolecularcr0000unse/page/472 .
• Book: Hendrickson WA, Ogata CM . Phase determination from multiwavelength anomalous diffraction measurements . 1997 . Macromolecular Crystallography Part A . 276 . 494–523 . 10.1016/S0076-6879(97)76074-9 . 27799111 . Methods in Enzymology . 978-0-12-182177-7 . https://archive.org/details/macromolecularcr0000unse/page/494 .
• Bella J, Rossmann MG . 1998 . A General Phasing Algorithm for Multiple MAD and MIR Data . Acta Crystallographica D. 54 . 2 . 159–174 . 10.1107/s0907444997010469 . 9761882 . 1998AcCrD..54..159B .
• Guss JM, Merritt EA, Phizackerley RP, Hedman B, Murata M, Hodgson KO, Freeman HC . Keith Hodgson . Hans Freeman . 1989 . Phase determination by multiple-wavelength X-ray diffraction: crystal structure of a basic blue copper protein from cucumbers . Science . 241 . 806–811 . 3406739 . 10.1126/science.3406739 . 4867. 1988Sci...241..806G .

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 . 10.1063/1.1142625. 1992RScI...63..850B .
• 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 . 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 . 799–804 . 9757093 . 10.1107/S0907444997018805 . Pt 5. 1998AcCrD..54..799S .
• SHELX - Book: Sheldrick GM . 1998 . SHELX: applications to macromolecules . Direct methods for solving macromolecular structures . S Fortier . 401–411 . Dordrecht: Kluwer Academic Publishers . 0-7923-4949-0.

Tutorials and examples

• Web site: The method of Multiple wavelength Anomalous Diffraction using Synchrotron Radiation at optimal X-ray energies: Application to Protein Crystallography . Gwyndaf . Evans . PhD Thesis . October 1994 . University of Warwick .

Notes and References

1. Book: Hendrickson W, Ogata C . Phase determination from multiwavelength anomalous diffraction measurements . Macromolecular Crystallography Part A . Methods in Enzymology . 276 . 494–523 . 1997 . 10.1016/S0076-6879(97)76074-9 . 27799111 . 978-0-12-182177-7 . https://archive.org/details/macromolecularcr0000unse/page/494 .
2. Hendrickson WA . 1985 . Analysis of Protein Structure from Diffraction Measurement at Multiple Wavelengths . Transactions of the ACA . 21.
3. Web site: Dictionary of common terms used in PHENIX . phenix-online.org . en . 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..