Drug off-target effects predicted using structural analysis in the context of a metabolic network model.

ABSTRACT: Recent advances in structural bioinformatics have enabled the prediction of protein-drug off-targets based on their ligand binding sites. Concurrent developments in systems biology allow for prediction of the functional effects of system perturbations using large-scale network models. Integration of these two capabilities provides a framework for evaluating metabolic drug response phenotypes in silico. This combined approach was applied to investigate the hypertensive side effect of the cholesteryl ester transfer protein inhibitor torcetrapib in the context of human renal function. A metabolic kidney model was generated in which to simulate drug treatment. Causal drug off-targets were predicted that have previously been observed to impact renal function in gene-deficient patients and may p

SUBMITTER: Chang RL 

PROVIDER: S-EPMC2950675 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature