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New publication: prediction of protein binding using in silico methods
Date: 20 Mar 2009
A new paper published in the journal Xenobiotica describes an investigation into in silico prediction of plasma and microsomal binding and its use in metabolic clearance determination. The article is entitled, ‘Utilization of estimated physicochemical properties as an integrated part of predicting hepatic clearance in the early drug-discovery stage: impact of plasma and microsomal binding.’
Metabolic stability assays performed using high-throughput screening techniques can be complicated by non-specific binding to microsomes. The authors evaluated various in silico approaches to predict the extent and variability of binding for 33 compounds documented in the literature.
Using several different models, physicochemical properties of each compound were calculated based on molecular structure and then used to estimate free fraction in both plasma (fuplasma) and microsomal incubations (fumic). These were then compared with observed results.
In both cases, the most accurate predictions were obtained with the Simcyp Simulator using physicochemical parameters calculated by ACDLabs software (SciFinder). These values were subsequently used in Simcyp simulations to predict blood clearance in a single individual for each compound.
From their investigations, the authors recognise the feasibility and usefulness of in silico methods in the prediction of hepatic clearance early on in drug discovery when measured values may not be available.
The study was conducted by Emoto et al. from the Showa Pharmaceutical University, Tokyo, and the University of Sheffield. Please click here for a link to the abstract and full text options.