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.