J Chem Inf Model - Conditional probabilistic analysis for prediction of the activity landscape and relative compound activities.

Tópicos

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Resumo

Structure-property relationships and structure-activity relationships play an important role in many research areas, such as medicinal chemistry and drug discovery. Such methods, however, have focused on providing post-hoc descriptions of such relationships based on known data. The ability for these descriptions to remain relevant when considering compounds of unknown activity, and thus the prediction of activity and property landscapes using existing data, remains little explored. In this study, we present a novel method of evaluating the ability of a compound comparison methodology to provide accurate information about a set of unknown compounds and also explore the ability of these predicted activity landscapes to prioritize active compounds over inactive. These methods are applied to three distinct and diverse sets of compounds, each with activity data for multiple targets, for a total of eight target-compound set pairs. Six methodologically distinct compound comparison methods were evaluated. We show that overall, all compound comparison methods provided an improvement in structure-activity relationship prediction over random and were able to prioritize compounds in a superior manner to random sampling, but the degree of success and therefore applicability varied markedly.

Resumo Limpo

structureproperti relationship structureact relationship play import role mani research area medicin chemistri drug discoveri method howev focus provid posthoc descript relationship base known data abil descript remain relev consid compound unknown activ thus predict activ properti landscap use exist data remain littl explor studi present novel method evalu abil compound comparison methodolog provid accur inform set unknown compound also explor abil predict activ landscap priorit activ compound inact method appli three distinct divers set compound activ data multipl target total eight targetcompound set pair six methodolog distinct compound comparison method evalu show overal compound comparison method provid improv structureact relationship predict random abl priorit compound superior manner random sampl degre success therefor applic vari mark

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