Title: Rational Principles of Compound Selection for Combinatorial Library Design
VOLUME: 5 ISSUE: 2
Author(s):Alexander Tropsha and Weifan Zheng
Affiliation:Laboratory for Molecular Modeling, Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Keywords:morphine, met-enkephalin, simulated annealing guided evaluation(sage)
Abstract: It is practically impossible in a short period of time to synthesize and test all compounds in any large exhaustive chemical library. We discuss rational approaches to selecting representative subsets of virtual libraries that help direct experimental synthetic efforts for both targeted and diverse library design. For targeted library design, we consider principles based on the similarity to lead molecules. In the case of diverse library design, we discuss algorithms aimed at the selection of both diverse and representative subsets of the entire chemical library space. We illustrate methodologies with several practical examples.
