This chapter discusses the preparation of isomorphous derivatives, which represents the main-research effort in protein structure laboratories at the present time. The chemical problem of combining compounds that contain atoms of high atomic number with crystalline proteins to form suitable derivatives is made more difficult by severely restrictive crystallographic criterion, if isomorphism must be satisfied. However, the applications of isomorphous replacement to fully determined protein structures shows great promise in the determination of protein function and more particularly enzyme function. This chapter explores that it is necessary to include a brief theoretical outline of the fundamental problem of protein crystallography and the method currently used in its solution, the practical aspects are the main concerns of this chapter.
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