Knowledge and Intelligence in Drug Design

Publisher Summary Ackoff and Emery's dual nature of knowledge provides a useful framework for the understanding of medicinal chemistry and how it enables chemists to be productive. Ackoff and Emery propose that knowledge consists of at least two different senses: possession of facts (or awareness of a state of affairs) and possession of skills. By considering drug design as a process, the core of medicinal chemistry knowledge can be abstracted as the possession of facts and the possession of skills. The possession of facts encompasses the knowledge gained by understanding the probability of predicted and observed properties of the chemical structure in relation to its desired properties. The possession of skills is the knowledge required to efficiently navigate the optimization path to achieve the desired balance of properties. Each new piece of information—whether the crystal structure of a drug bound to a protein or the identification of a labile site of reactive metabolite, or the general physicochemical properties of drug-space—further restricts our hypothesis space in drug design. Practical skills such as the mastery of design tactics or parallel chemistry methods help the medicinal chemists efficiently navigate a pathway through hypothesis space. Therefore, by understanding and formalizing how knowledge is generated and used in medicinal chemistry, a methodology to rationally improve the efficiency and effectiveness of drug designs can be developed.