Identification and selection of "privileged fragments" suitable for primary screening.
The use of small molecule libraries for fragment-based primary screening (FBS) is a well-known approach to identify protein binders in the low affinity range. However, the search, analysis, and selection of suitable screening fragments can be a lengthy process, because of the large number of compounds that must be analyzed for different levels of ring/substituents identification and submitted to selection/exclusion criteria based on their physicochemical properties. The purpose of the present work is to propose a strategy to identify substructures from databases of known drugs, which can be used as templates for the generation of libraries of "privileged fragments" that are able to provide high-quality hits. The entire process has been developed integrating Pipeline Pilot (Accelrys Inc., San Diego, CA; http://www.accelrys.com ) native components and user-defined molecular files containing ISIS-like substructure query features (Symyx, San Ramon, CA; http://www.symyx.com ). The method is effortless, easy to put in place, and fast enough to be iteratively applied to different sources of druglike compounds.
Gianti
Eleonora
E
Computational Sciences Group, Department of Chemistry (Congenia s.r.l.), Genextra S.p.A., Milan MI 20100, Italy.
Sartori
Luca
L
D000465:Algorithms; D055598:Chemical Phenomena; D016000:Cluster Analysis; D016208:Databases, Factual; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical / Q000706:statistics & numerical data*; D048088:Informatics; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012985:Software Design
D004364:Pharmaceutical Preparations