Members of the EF-hand protein superfamily (1) share a common calciumbinding helix-loop-helix motif as a building block, whose conformation essentially determines biological function. It has been well demonstrated that specific binding of Ca2+to the loop alters conformation of the motif, involving rearrangement of the two helices of the EF-hand in three-dimensional (3-D) space (reviewed in refs. 2–4. In Ca2+-sensor proteins within this superfamily, the Ca2+-induced conformational change is responsible for the sensor activity (2). For many years this change has been quantitatively characterized by the interhelical angle measured between the two helices (5–9). Recently, Nelson and Chazin (10) reported an interaction-based analysis for examining conformational change in EF-hand proteins, including computation of distance difference matrices (calculated between each pair of Cα atoms in two structures). Both methods have advantages and disadvantages. The former approach gives a single, descriptive parameter for a given EF-hand, but is obviously insufficient to describe the conformation and its change in detail. The latter approach is more comprehensive and is sensitive to small conformational changes, but yields a large number of parameters to be interpreted by the user. In this chapter, we describe a method termed Vector Geometry Mapping (VGM), an extension of the "interhelical angle"approach, which produces amore complete and descriptive picture of EF-hand conformations.
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