De novo design - hop(p)ing against hope.
Current trends in computational de novo design provide a fresh approach to 'scaffold-hopping' in drug discovery. The methodological repertoire is no longer limited to receptor-based methods, but specifically ligand-based techniques that consider multiple properties in parallel, including the synthetic feasibility of the computer-generated molecules and their polypharmacology, provide innovative ideas for the discovery of new chemical entities. The concept of fragment-based and virtual reaction-driven design enables rapid compound optimization from scratch with a manageable complexity of the search. Starting from known drugs as a reference, such algorithms suggest drug-like molecules with motivated scaffold variations, and advanced mathematical models of structure-activity landscapes and multi-objective design techniques have created new opportunities for hit and lead finding.
Gisbert
G
Schneider
D015195:Drug Design; D008024:Ligands; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry; D013329:Structure-Activity Relationship
D008024:Ligands; D004364:Pharmaceutical Preparations