Computational studies of ligand/receptor interactions.
An analysis of common features of many proteins provided the basis for a general model for the origin of receptors (Topiol, 1987). In this model, receptors are derived from fully operational parent systems. The parent system is rendered inactive by "deletion" of some critical component, thereby converting it to a receptor for the deleted entity. Such a model could explain the use of common molecular machinery by different biological systems (e.g., receptors and enzymes), the origin of receptor subtypes, the use of common effector systems by different receptors, the sequence homologies between varied proteins, the relationship between endogenous ligands and biological "building blocks", and the selectivity and compatibility between natural receptors and endogenous ligands. Some examples of the use of this model to analyze a number of different biochemical systems and processes will be given. Preliminary insights from these studies as a guide to developing molecular models for the action of cyclic nucleotide second messengers will be discussed.
Topiol
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Department of Medicinal Chemistry, Berlex Laboratories, Inc., Cedar Knolls, NJ 07927.
Sabio
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D002384:Catalysis; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D015195:Drug Design; D008024:Ligands; D008956:Models, Chemical; D011955:Receptors, Drug / Q000378:metabolism*
D008024:Ligands; D011955:Receptors, Drug; D000242:Cyclic AMP; D006152:Cyclic GMP