A multi-variant, viral dynamic model of genotype 1 HCV to assess the in vivo evolution of protease-inhibitor resistant variants.

Variants resistant to compounds specifically targeting HCV are observed in clinical trials. A multi-variant viral dynamic model was developed to quantify the evolution and in vivo fitness of variants in subjects dosed with monotherapy of an HCV protease inhibitor, telaprevir. Variant fitness was estimated using a model in which variants were selected by competition for shared limited replication space.

Rapid decrease of wild-type hepatitis C virus on telaprevir treatment.

Background: Telaprevir (TVR) is a hepatitis C virus (HCV) NS3.4A protease inhibitor that has exhibited antiviral activity in patients with HCV genotype 1 infection. The viral dynamics in patients dosed with TVR were compared with those reported for patients treated with interferon (IFN).

Classifying protein kinase structures guides use of ligand-selectivity profiles to predict inactive conformations: structure of lck/imatinib complex.

We report a clustering of public human protein kinase structures based on the conformations of two structural elements, the activation segment and the C-helix, revealing three discrete clusters. One cluster includes kinases in catalytically active conformations. Each of the other clusters contains a distinct inactive conformation.

CORES: an automated method for generating three-dimensional models of protein/ligand complexes.

We describe a new, automated method for building 3D models of small-molecule ligands complexed with proteins. Modeling templates are constructed from frameworks (i.e.