Multiple anomalous diffraction

The effect is particularly useful for structure determinations of macromolecules where multiple anomalous diffraction (MAD) experiments are combined to yield the phase factors necessary to obtain the electron density mapping. 

A teclmique that employs principles similar to those of isomorphous replacement is multiple-wavelength anomalous diffraction (MAD) [27]. The expression for the atomic scattering factor in equation (B1.8.2h) is strictly accurate only if the x-ray wavelength is well away from any characteristic absorption edge of the element, in which case the atomic scattering factor is real and Filiki) = Fthkl V- Since the diffracted... 

The intensity differences obtained in the diffraction pattern by illuminating such a crystal by x-rays of different wavelengths can be used in a way similar to the method of multiple isomorphous replacement to obtain the phases of the diffracted beams. This method of phase determination which is called Multiwavelength Anomalous Diffraction, MAD, and which was pioneered by Wayne Hendrickson at Columbia University, US, is now increasingly used by protein cystallographers. 

Ealick, S.E. (2000) Advances in multiple wavelength anomalous diffraction crystallography, Curr. Opin. Chem. Biol., 4, 495-499. 

The multiple-wavelength anomalous diffraction method (MAD) relies upon sufficiently strong anomalously scattering atoms in the protein structure itself In this method, diffraction data must be collected at a number of different wavelengths, usually requiring data collection with... 

From a relatively small begiiming, nearly two decades ago (Guss et al., 1988 Murthy et al., 1988 Hendrickson et al., 1988, 1989), phase calculation using Multiple-wavelength Anomalous Diffraction (MAD) data has become more widespread and generally used. There are many reviews that cover diverse aspects of the process (Hendrickson, 1991 Smith, 1991 Ogata, 1998 Ealick, 2000). This review will concentrate on the most recent developments and experimental details, and is essentially an update to the author s earlier review (Krishna Murthy, 1996). 

Krishna Murthy H. M. (1996). The use of multiple wavelength anomalous diffraction in ab initio phase determination. Method Mol. Biol. 56,127-152. 

La Fortelle, E. D. and Bricogne, G. (1997). Maximum-likelihood heavy-atom parameter refinement for multiple isomorphous replacement and multiwavelength anomalous diffraction methods. Method Enzymol. 276, 472 94. 

Ramakrishnan, V. and Biou, V. (1997). Treatment of multiwavelength anomalous diffraction data as a special case of multiple isomorphous replacement. Method Enzymol. 276, 538-557. 

Alternative methods of solving the phase problem are also used now. When a transition metal such as Fe, Co, or Ni is present in the protein, anomolous scattering of X-rays at several wavelengths (from synchrotron radiation) can be used to obtain phases. Many protein structures have been obtained using this multiple wavelength anomalous diffraction (MAD phasing) method.404 407 408 Selenocysteine is often incorporated into a protein that may be produced in... 

X-ray crystallography is currently the most powerful analytical method by which three-dimensional structure information on biological macromolecules may be obtained at high resolution. Its application is however limited first by the preparation of single crystals suitable for X-ray diffraction and second by the so-called phase problem , that is the calculation of phases of difBaction data. Several approaches are available in order to circumvent this latter problem. The most commonly used methods are the multiple and single isomorphous replacement (MIR, SIR). These methods, as well as multiple anomalous difBaction (MAD), require the preparation of heavy atom derivatives, usually by the introduction of electron-dense atoms at distinct locations of the crystal lattice. This is usually done by crystal soaking experiments. 

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