Structure-Activity Relationship & Computer-Aided Drug Design

Introduction & scope

• Structure-Activity Relationship (SAR) — the empirical & quantitative study of how changes in a compound's chemical structure (scaffold + substituents) alter its biological activity — potency, selectivity & other properties — against a target. SAR is built by synthesising/buying a series of analogues of a hit and testing each.
• CADD — Computer-Aided Drug Design / Discovery — use of in-silico methods (molecular simulation, docking, similarity searching, structure prediction, machine learning) to model compound–target interactions and design/prioritise tight-binding ligands. In silico = an experiment done by computer, complementary to in vivo / in vitro.
• Two-faceted topic — SAR is the medicinal-chemistry / lead-optimisation side; CADD is the computational engine that increasingly drives both ligand discovery & SAR interpretation. Both sit inside the broader drug-discovery pipeline.
• "Invented, not discovered" — "drug discovery" fits natural compounds, but most modern drugs are wholly new molecules painstakingly optimised against many criteria — an interplay of design & experiment — so they are "more invented than discovered".
• Enabling advances — CADD became practical from the 1980s via two parallels: high-resolution 3-D protein structures (X-ray crystallography — Hodgkin/Kendrew/Perutz) + the rise of computing power for simulation & visualisation.