J Chem Inf Model - Using novel descriptor accounting for ligand-receptor interactions to define and visually explore biologically relevant chemical space.

Tópicos

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

Resumo

The definition and pragmatic implementation of biologically relevant chemical space is critical in addressing navigation strategies in the overlapping regions where chemistry and therapeutically relevant targets reside and, therefore, also key to performing an efficient drug discovery project. Here, we describe the development and implementation of a simple and robust method for representing biologically relevant chemical space as a general reference according to current knowledge, independently of any reference space, and analyzing chemical structures accordingly. Underlying our method is the generation of a novel descriptor (LiRIf) that converts structural information into a one-dimensional string accounting for the plausible ligand-receptor interactions as well as for topological information. Capitalizing on ligand-receptor interactions as a descriptor enables the clustering, profiling, and comparison of libraries of compounds from a chemical biology and medicinal chemistry perspective. In addition, as a case study, R-groups analysis is performed to identify the most populated ligand-receptor interactions according to different target families (GPCR, kinases, etc.), as well as to evaluate the coverage of biologically relevant chemical space by structures annotated in different databases (ChEMBL, Glida, etc.).

Resumo Limpo

definit pragmat implement biolog relev chemic space critic address navig strategi overlap region chemistri therapeut relev target resid therefor also key perform effici drug discoveri project describ develop implement simpl robust method repres biolog relev chemic space general refer accord current knowledg independ refer space analyz chemic structur accord under method generat novel descriptor lirif convert structur inform onedimension string account plausibl ligandreceptor interact well topolog inform capit ligandreceptor interact descriptor enabl cluster profil comparison librari compound chemic biolog medicin chemistri perspect addit case studi rgroup analysi perform identifi popul ligandreceptor interact accord differ target famili gpcr kinas etc well evalu coverag biolog relev chemic space structur annot differ databas chembl glida etc

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