title: Structure-based library design in efficient discovery of novel inhibitors.
abstract: Structure-based library design employs both structure-based drug design (SBDD) and combinatorial library design. Combinatorial library design concepts have evolved over the past decade, and this chapter covers several novel aspects of structure-based library design together with successful case studies in the anti-viral drug design HCV target area. Discussions include reagent selections, diversity library designs, virtual screening, scoring/ranking, and post-docking pose filtering, in addition to the considerations of chemistry synthesis. Validation criteria for a successful design include an X-ray co-crystal complex structure, in vitro biological data, and the number of compounds to be made, and these are addressed in this chapter as well.
authors.affiliation: Drug Design Consulting, Irvine, CA, USA. yshunqi@gmail.com
authors.forename: Shunqi
authors.initials: S
authors.lastname: Yan
authors.forename: Robert
authors.initials: R
authors.lastname: Selliah
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology; D007202:Indicators and Reagents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D011487:Protein Conformation; D015203:Reproducibility of Results; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013449:Sulfonamides / Q000737:chemistry; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015898:Tomography Scanners, X-Ray Computed; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D054852:Small Molecule Libraries; D013449:Sulfonamides; D013844:Thiazoles; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase