Backward binding and other structural surprises

From simple to highly complex molecules, examples are cited of ‘backward’ or retro-binding. In some cases, symmetry dictates the directions observed and in cases not treated here, statistical disorder reveals averaged forward/backward binding. In most of the cases found, both the receptor and the ligand(s) are asymmetric, so local interactions dictate the preferred binding mode. A general rationale is presented to explain some of these observations and a hypothesis derived from this review can be tested experimentally.

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