J Chem Inf Model - FAst MEtabolizer (FAME): A rapid and accurate predictor of sites of metabolism in multiple species by endogenous enzymes.

Tópicos

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Resumo

FAst MEtabolizer (FAME) is a fast and accurate predictor of sites of metabolism (SoMs). It is based on a collection of random forest models trained on diverse chemical data sets of more than 20000 molecules annotated with their experimentally determined SoMs. Using a comprehensive set of available data, FAME aims to assess metabolic processes from a holistic point of view. It is not limited to a specific enzyme family or species. Besides a global model, dedicated models are available for human, rat, and dog metabolism; specific prediction of phase I and II metabolism is also supported. FAME is able to identify at least one known SoM among the top-1, top-2, and top-3 highest ranked atom positions in up to 71%, 81%, and 87% of all cases tested, respectively. These prediction rates are comparable to or better than SoM predictors focused on specific enzyme families (such as cytochrome P450s), despite the fact that FAME uses only seven chemical descriptors. FAME covers a very broad chemical space, which together with its inter- and extrapolation power makes it applicable to a wide range of chemicals. Predictions take less than 2.5 s per molecule in batch mode on an Ultrabook. Results are visualized using Jmol, with the most likely SoMs highlighted.

Resumo Limpo

fast metabol fame fast accur predictor site metabol som base collect random forest model train divers chemic data set molecul annot experiment determin som use comprehens set avail data fame aim assess metabol process holist point view limit specif enzym famili speci besid global model dedic model avail human rat dog metabol specif predict phase ii metabol also support fame abl identifi least one known som among top top top highest rank atom posit case test respect predict rate compar better som predictor focus specif enzym famili cytochrom ps despit fact fame use seven chemic descriptor fame cover broad chemic space togeth inter extrapol power make applic wide rang chemic predict take less s per molecul batch mode ultrabook result visual use jmol like som highlight

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