J Chem Inf Model - In silico deconstruction of ATP-competitive inhibitors of glycogen synthase kinase-3?.

Tópicos

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Resumo

Fragment-based methods have emerged in the last two decades as alternatives to traditional high throughput screenings for the identification of chemical starting points in drug discovery. One arguable yet popular assumption about fragment-based design is that the fragment binding mode remains conserved upon chemical expansion. For instance, the question of the binding conservation upon fragmentation of a molecule is still unclear. A number of papers have challenged this hypothesis by means of experimental techniques, with controversial results, "underlining" the idea that a simple generalization, maybe, is not possible. From a computational standpoint, the issue has been rarely addressed and mostly to test novel protocols on limited data sets. To fill this gap, we here report on a computational retrospective study concerned with the in silico deconstruction of leadlike compounds, active on the pharmaceutically relevant enzyme glycogen synthase kinase-3?.

Resumo Limpo

fragmentbas method emerg last two decad altern tradit high throughput screen identif chemic start point drug discoveri one arguabl yet popular assumpt fragmentbas design fragment bind mode remain conserv upon chemic expans instanc question bind conserv upon fragment molecul still unclear number paper challeng hypothesi mean experiment techniqu controversi result underlin idea simpl general mayb possibl comput standpoint issu rare address most test novel protocol limit data set fill gap report comput retrospect studi concern silico deconstruct leadlik compound activ pharmaceut relev enzym glycogen synthas kinas

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