DRUGS AS CHEMICAL MESSAGES - MOLECULAR-STRUCTURE, BIOLOGICAL CONTEXT AND STRUCTURE-ACTIVITY-RELATIONSHIPS

This essay offers a broad description of molecular structure by integr ating form (geometry), function (properties) and fluctuation to form a property space. Transactions between compounds and their molecular en vironments are then shown to Lead to complex systems with emergent pro perties. Complex systems of this type become pharmacologically relevan t when the molecular environment is a biological target such as a memb rane, a receptor or an enzyme, all of which have their own property sp ace. When a drug and a target interact, their transactions are seen as mutual influences with the target recognizing one or a few molecular states of the drug, and the drug modifying some properties in the targ et. A functional response is an emergent property of some drug-target complex systems, implying that the information to produce a functional response is contained neither in the message (the drug) alone, nor in the biological target (the context) alone. These conceptual views can affect our perception of structure-activity relationships, and it-is suggested that relations between activity and property space might be worth exploring, The amplitude of the property space of the target may account for fuzzy relations, whereas diversity of interactions may pr oduce discontinuous SAR.