Lauria A
University of Palermo
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Lauria A.
Journal of Molecular Graphics & Modelling | 2009
Lauria A; Mario Ippolito; Anna Maria Almerico
During the last few decades, the development of new anticancer strategies had to face the instability of many tumors, occurring when the genetic plasticity of cells produces new drug-resistant cancers. It has been shown that a chaperone protein, heat shock protein 90 (Hsp90), is one of the fundamental factors involved in the cell response to stresses, and its role in many biochemical pathways has been demonstrated. Thus, the inhibition of Hsp90 represents a new target of antitumor therapy, since it may influence many specific signaling pathways. The natural antibiotic Geldanamycin is the first Hsp90 inhibitor that has been identified. Nevertheless, more potent and water-soluble small molecules are currently in development, and many X-ray crystallographic structures of Hsp90-inhibitor complexes are available for drug discovery purposes. Here we used the complexes of Hsp90 with eight different ligands, belonging to several chemical classes, to perform molecular docking experiments, using a novel technique called induced fit. Through this approach, it was possible to take into account the flexibility of the residues in the active site and to maintain a high level of precision in docking algorithms. The results allowed to identify several conserved residues involved in the interaction between Hsp90 and its inhibitor. Moreover, the exposition of the active site to solvent allows many water molecules to insert within the complex, providing additional hydrogen and polar interactions. Our models also provided template structures for further experiments and reproduces with a good degree of reliability, the conformations of the inhibitors as observed in experimental structures.
Current Computer - Aided Drug Design | 2007
Anna Maria Almerico; Marco Tutone; Mario Ippolito; Lauria A
The treatment regimens for the HIV-1 have mainly included reverse transcriptase or protease inhibitors but their long-term clinical utility is limited by severe side effects and viral drug resistance. A new attractive target for chemotherapeutic intervention can be the Integrase enzyme, that mediates the integration of HIV-1 DNA into a host chromosome, for which there is no known counterparts in the host cell. A number of derivatives have been found to inhibit IN in in vitro assays, but no successful drug based on them has emerged so far, although many compounds have been proposed. Moreover most of the inhibitors do not belong to a very precise structural class: this fact makes these compounds a suitable target to be approached by all QSAR methods (classical and 3D) which therefore have been used to study the IN inhibitors. This review focuses on the molecular basis and rationale for developing integrase inhibitors and assesses the literature results of the chemometric study on classes of these inhibitors. Rational drug design by mean of the pharmacophore approach, rigid and flexible docking methods, and de novo design contributed to the identification of the most promising class of inhibitors, the DKAs. Moreover molecular dynamics studies were included since they can contribute to give further insight into the inhibitors binding modes already explored by means of the docking simulations.
Qsar & Combinatorial Science | 2009
Lauria A; Mario Ippolito; Anna Maria Almerico
Journal of Molecular Modeling | 2007
Lauria A; Mario Ippolito; Anna Maria Almerico
Journal of Molecular Structure-theochem | 2007
Lauria A; Chiara Patella; Mario Ippolito; Anna Maria Almerico
Archive | 2011
Anna Maria Almerico; Antonino Lauria; Alessio Terenzi; Giampaolo Barone; Riccardo Bonsignore; Barone G; Almerico Am; Lauria A
Archive | 2009
Anna Maria Almerico; Lauria A; Mario Ippolito; Francesco Mingoia
Archive | 2009
Anna Maria Almerico; Lauria A; Marco Tutone; Mario Ippolito; Francesco Mingoia
Archive | 2008
Anna Maria Almerico; Antonino Lauria; Mario Ippolito; Lauria A; Ippolito M; Almerico Am
Archive | 2007
Gaetano Dattolo; Anna Maria Almerico; Antonino Lauria; Chiara Patella; Lauria A; Patella C; Almerico Am