A geometry force field which converts low-resolution X-ray models to structures with properties found at ultra high resolution.

A geometry optimization force field was developed using ultra high-resolution structures and tested using high- and low-resolution X-ray structures. Protein and small molecule X-ray data was used. When applied to ultra high-resolution structures the force field conserves the internal geometry and local strain energy.

Identification of novel small-molecule inducers of fetal hemoglobin using pharmacophore and 'PSEUDO' receptor models.

Pharmacologic reinduction of the developmentally silenced fetal (gamma) globin genes has been achieved in hemoglobinopathy patients using short chain fatty acid derivatives, with therapeutic effects. However, higher-potency inducers than are available in currently identified short chain fatty acid derivatives are desirable for long-term use. Using several short-chain fatty acids with established gamma-globin induction activity, a pharmacophore template was constructed with the TFIT module of the flo software and used to select several new candidate compounds, three of which exhibited significant activity in a gamma-globin gene reporter transcriptional assay which detects only strong inducers.

Assessment of docking poses: interactions-based accuracy classification (IBAC) versus crystal structure deviations.

Six docking programs (FlexX, GOLD, ICM, LigandFit, the Northwestern University version of DOCK, and QXP) were evaluated in terms of their ability to reproduce experimentally observed binding modes (poses) of small-molecule ligands to macromolecular targets. The accuracy of a pose was assessed in two ways: First, the RMS deviation of the predicted pose from the crystal structure was calculated. Second, the predicted pose was compared to the experimentally observed one regarding the presence of key interactions with the protein.