title: Structure-based combinatorial library design: methodologies and applications.
abstract: Rational design of small focused libraries that are biased toward specific therapeutic targets is currently at the forefront of combinatorial library design. Various structure-based design strategies can be implemented in focused library design when the 3D structure of the target is available through X-ray or NMR determination. This review discusses the major methods and programs specifically developed for the purpose of designing combinatorial libraries under the constraint of the binding site of a biological target, with emphasis on their advantages and disadvantages. Examples of the successful application of these methodologies are highlighted, demonstrating their performances within the practical drug discovery process.
authors.affiliation: Computer Assisted Drug Discovery, R.W. Johnson Pharmaceutical Research Institute, Raritan, NJ 08869, USA.
authors.forename: Mary Pat
authors.initials: MP
authors.lastname: Beavers
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
mesh_terms: D001665:Binding Sites; D002626:Chemistry, Pharmaceutical; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D019151:Peptide Library; D011480:Protease Inhibitors / Q000737:chemistry; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D019151:Peptide Library; D011480:Protease Inhibitors