Romano T. Kroemer

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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)
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)
A large-scale evaluation and comparison of four cavity detection algorithms was carried out. The algorithms SiteFinder, fpocket, PocketFinder, and SiteMap were evaluated on a protein test set containing 5416 protein-ligand complexes and 9900 apo forms, corresponding to a subset of the set used earlier for benchmarking the PocketFinder algorithm. For the(More)
The implementation of a structure based virtual affinity maturation protocol and evaluation of its predictivity are presented. The in silico protocol is based on conformational sampling of the interface residues (using the Dead End Elimination/A* algorithm), followed by the estimation of the change of free energy of binding due to a point mutation, applying(More)
The steric descriptors commonly used in CoMFA--Lennard-Jones 6-12 potential-derived interaction energies calculated between a probe atom and the molecules under investigation--have been replaced by variables indicating the presence of an atom of a particular molecule in predefined volume elements (cubes) within the region enclosing the ensemble of(More)
Investigations into the conformational behaviour of macrocyclic ligands 5 and 6 derived from (R,R)-1,2-diaminocyclohexane have been undertaken using molecular modelling, single crystal X-ray diffraction and variable temperature 1H NMR spectroscopy. These have revealed that the lowest energy conformers in both cases do not possess the expected C2-element of(More)
Comparative molecular field analysis (CoMFA) is a three-dimensional quantitative structure-activity relationship (3D-QSAR) method which correlates precalculated fields surrounding a set of molecules with some target property. Among others, the electrostatic fields are commonly used. These are usually generated by calculating the Coulomb potential between a(More)
A new automated procedure to improve the predictive quality of CoMFA models for both training and test sets is described. A model of greater consistency is generated by performing small reorientations of the underlying molecules for which too low activities are calculated. In order to predict activities of test compounds, the most similar molecules in the(More)
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