Rational Drug Design

Rational drug design is the hypothesis-driven approach to compound design in which chemical structures are proposed on the basis of a defined understanding...

Rational drug design is the hypothesis-driven approach to compound design in which chemical structures are proposed on the basis of a defined understanding of the target's biological function and three-dimensional structure, in direct contrast to earlier empirical or random-screening approaches to drug discovery. Rational design typically follows one of two complementary strategies depending on the information available: structure-based design, applied when a resolved three-dimensional structure of the target is available, and ligand-based design, applied when only the structures of known active compounds, rather than the target itself, are available. The unifying principle of rational design is that a specific, testable structural hypothesis — rather than an empirical screening outcome alone — guides each design decision, allowing medicinal chemists to propose chemically reasoned modifications rather than proceeding by trial and error.