title: Serendipity meets precision: the integration of structure-based drug design and combinatorial chemistry for efficient drug discovery.
abstract: Structure-based drug design uses three-dimensional visualization of drug candidates bound to a target receptor to direct structural modifications that increase potency. This widely used approach is limited by the difficulty of accurately predicting drug-binding affinities from three-dimensional structures. The integration of structure-based drug design with combinatorial chemistry can overcome this limitation by providing an empirical understanding of drug-binding energies. This integration allows compound synthesis and evaluation in parallel, and also helps assure that the compounds produced have properties consistent with good bioavailability and safety.
authors.affiliation: 3-Dimensional Pharmaceuticals, Inc., Eagleview Corporate Center, 665 Stockton Drive, Suite 104, Exton, PA 19341, USA. salemme@3dp.com
authors.forename: F R
authors.initials: FR
authors.lastname: Salemme
authors.forename: J
authors.initials: J
authors.lastname: Spurlino
authors.forename: R
authors.initials: R
authors.lastname: Bone
mesh_terms: D001682:Biological Availability; D003198:Computer Simulation; D015195:Drug Design; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism; D012449:Safety; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors
chemical_list: D004364:Pharmaceutical Preparations; D011955:Receptors, Drug; D015842:Serine Proteinase Inhibitors; D013917:Thrombin