J Chem Inf Model - Mining for bioactive scaffolds with scaffold networks: improved compound set enrichment from primary screening data.

Tópicos

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{ detect(2391) sensit(1101) algorithm(908) }

Resumo

Identification of meaningful chemical patterns in the increasing amounts of high-throughput-generated bioactivity data available today is an increasingly important challenge for successful drug discovery. Herein, we present the scaffold network as a novel approach for mapping and navigation of chemical and biological space. A scaffold network represents the chemical space of a library of molecules consisting of all molecular scaffolds and smaller "parent" scaffolds generated therefrom by the pruning of rings, effectively leading to a network of common scaffold substructure relationships. This algorithm provides an extension of the scaffold tree algorithm that, instead of a network, generates a tree relationship between a heuristically rule-based selected subset of parent scaffolds. The approach was evaluated for the identification of statistically significantly active scaffolds from primary screening data for which the scaffold tree approach has already been shown to be successful. Because of the exhaustive enumeration of smaller scaffolds and the full enumeration of relationships between them, about twice as many statistically significantly active scaffolds were identified compared to the scaffold-tree-based approach. We suggest visualizing scaffold networks as islands of active scaffolds.

Resumo Limpo

identif meaning chemic pattern increas amount highthroughputgener bioactiv data avail today increas import challeng success drug discoveri herein present scaffold network novel approach map navig chemic biolog space scaffold network repres chemic space librari molecul consist molecular scaffold smaller parent scaffold generat therefrom prune ring effect lead network common scaffold substructur relationship algorithm provid extens scaffold tree algorithm instead network generat tree relationship heurist rulebas select subset parent scaffold approach evalu identif statist signific activ scaffold primari screen data scaffold tree approach alreadi shown success exhaust enumer smaller scaffold full enumer relationship twice mani statist signific activ scaffold identifi compar scaffoldtreebas approach suggest visual scaffold network island activ scaffold

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