SIR, SAD, MAD, DM: Integrated Methods
For a long time the method of isomorphous replacement has been the only method used to solve the phase problem in protein crystallography. Starting with a native protein crystal, of which a reflection data set has been measured (leading to |FP i|, an abbreviation for |Fhi P|), this crystal is soaked in a solution of a heavy-atom salt for a day, a week, or perhaps for even longer. What one hopes for is that a heavy atom will attach to a protein molecule in a specific way (i.e. identically in a great number of unit cells) without changing (i.e. less than 0.5%) the geometry of the unit cell. Subsequently a reflection dataset of the alleged heavy-atom derivative is collected (leading to values for |Fi HP|).
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