Reviewing the pros and cons of protein structure-based pharmacophore modelling

20 Dec 2011

Pharmacophore modelling is a useful tool for medicinal chemists to identify novel ligands to bind to a receptor. This review from Chris de Graaf and colleagues describes the advantages, and challenges, of using 3D protein structures to predict pharmacophores (rather than using a ligand-based approach, which involves searching for similarities based on previously known active ligands).

The review covers (i) protein structure preparation, (ii) binding site detection, (iii) pharmacophore feature definition, and (iv) pharmacophore feature selection, concluding that ‘SBPs are valuable tools for hit and lead optimization, compound library design and target hopping, especially in cases where ligand information is scarce‘.