Paola Bisignano

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The idea of sodium ions altering G-protein-coupled receptor (GPCR) ligand binding and signaling was first suggested for opioid receptors (ORs) in the 1970s and subsequently extended to other GPCRs. Recently published ultra-high-resolution crystal structures of GPCRs, including that of the δ-OR subtype, have started to shed light on the mechanism underlying(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)
MOTIVATION A large fraction of the entries contained in the Protein Data Bank describe proteins in complex with low molecular weight molecules such as physiological compounds or synthetic drugs. In many cases, the same molecule is found in distinct protein-ligand complexes. There is an increasing interest in Medicinal Chemistry in comparing protein binding(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)
With the hope of discovering effective analgesics with fewer side effects, attention has recently shifted to allosteric modulators of the opioid receptors. In the past two years, the first chemotypes of positive or silent allosteric modulators (PAMs or SAMs, respectively) of μ- and δ-opioid receptor types have been reported in the literature. During a(More)
The idea of sodium ions altering G-protein-coupled receptor (GPCR) ligand binding and signaling was first suggested for opioid receptors (ORs) in the 1970s and subsequently extended to other GPCRs. Recently published ultra-high-resolution crystal structures of GPCRs, including that of the δ-OR subtype, have started to shed light on the mechanism underlying(More)
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