Angelo D. Favia

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Most function prediction methods that identify cognate ligands from binding site analyses work on the assumption of molecular complementarity. These approaches build on the conjectured complementarity of geometrical and physicochemical properties between ligands and binding sites so that similar binding sites will bind similar ligands. We found that this(More)
Our main objective was to compile a data set of high-quality protein-fragment complexes and make it publicly available. Once assembled, the data set was challenged using docking procedures to address the following questions: (i) Can molecular docking correctly reproduce the experimentally solved structures? (ii) How thorough must the sampling be to(More)
Small molecules used in fragment-based drug discovery form multiple, promiscuous binding complexes difficult to capture experimentally. Here, we identify such binding poses and their associated energetics and kinetics using molecular dynamics simulations on AmpC β-lactamase. Only one of the crystallographic binding poses was found to be thermodynamically(More)
Fragment-based methods have emerged in the last two decades as alternatives to traditional high throughput screenings for the identification of chemical starting points in drug discovery. One arguable yet popular assumption about fragment-based design is that the fragment binding mode remains conserved upon chemical expansion. For instance, the question of(More)
This paper deals with a novel computational approach that aims to measure the similarities of protein binding sites through comparison of atomic grid maps. The assessment of structural similarity between proteins is a longstanding goal in biology and in structure-based drug design. Instead of focusing on standard structural alignment techniques, mostly(More)
The design of multitarget-directed ligands is a promising strategy for discovering innovative drugs. Here, we report a mechanistic study that clarifies key aspects of the dual inhibition of the fatty acid amide hydrolase (FAAH) and the cyclooxygenase (COX) enzymes by a new multitarget-directed ligand named ARN2508(More)
In humans, type 1 11β-hydroxysteroid dehydrogenase (11β-HSD-1) plays a key role in the regulation of the glucocorticoids balance by converting the inactive hormone cortisone into cortisol. Numerous functional aspects of 11β-HSD-1 have been understood thanks to the availability at the Worldwide Protein Data Bank of a number of X-ray structures of the enzyme(More)
The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone to the active glucocorticoid cortisol, thereby acting as a cellular switch to mediate glucocorticoid action in many tissues. Several studies have indicated that 11beta-HSD1 plays a crucial role in the onset of type 2 diabetes and central obesity. As a consequence,(More)
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