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PASS (Putative Active Sites with Spheres) is a simple computational tool that uses geometry to characterize regions of buried volume in proteins and to identify positions likely to represent binding sites based upon the size, shape, and burial extent of these volumes. Its utility as a predictive tool for binding site identification is tested by predicting(More)
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(More)
Target-focused compound libraries are collections of compounds which are designed to interact with an individual protein target or, frequently, a family of related targets (such as kinases, voltage-gated ion channels, serine/cysteine proteases). They are used for screening against therapeutic targets in order to find hit compounds that might be further(More)
Novel scoring functions that predict the affinity of a ligand for its receptor have been developed. They were built with several statistical tools (partial least squares, genetic algorithms, neural networks) and trained on a data set of 100 crystal structures of receptor-ligand complexes, with affinities spanning 10 log units. The new scoring functions(More)
The ability to accurately predict biological affinity on the basis of in silico docking to a protein target remains a challenging goal in the CADD arena. Typically, "standard" scoring functions have been employed that use the calculated docking result and a set of empirical parameters to calculate a predicted binding affinity. To improve on this, we are(More)
Solubility data for 930 diverse compounds have been analyzed using linear Partial Least Square (PLS) and nonlinear PLS methods, Continuum Regression (CR), and Neural Networks (NN). 1D and 2D descriptors from MOE package in combination with E-state or ISIS keys have been used. The best model was obtained using linear PLS for a combination between 22 MOE(More)
One of the interesting puzzles of amyloid beta-peptide of Alzheimer's disease (Abeta) is that it appears to polymerize into amyloid fibrils in a parallel beta sheet topology, while smaller subsets of the peptide produce anti-parallel beta sheets. In order to target potential weak points of amyloid fibrils in a rational drug design effort, it would be(More)
Cyclin-dependent kinases (CDKs) play a key role in regulating the cell cycle. The cyclins, their activating agents, and endogenous CDK inhibitors are frequently mutated in human cancers, making CDKs interesting targets for cancer chemotherapy. Our aim is the discovery of selective CDK4/cyclin D1 inhibitors. An ATP-competitive pyrazolopyrimidinone CDK(More)