Notes in Pure Mathematics & Mathematical Structures in Physics

These Notes deal with various areas of mathematics, and seek reciprocal combinations, explore mutual relations, ranging from abstract objects to problems in physics.Comment: Small improvements and addition

Cold Denaturation Unveiled: Molecular Mechanism of the Asymmetric Unfolding of Yeast Frataxin

none5Sanfelice, Domenico; Morandi, Edoardo; Pastore, Annalisa; Niccolai, Neri; Temussi, Piero AndreaSanfelice, Domenico; Morandi, Edoardo; Pastore, Annalisa; Niccolai, Neri; Temussi, Piero Andre

Transient Pockets and Surface Hotspots Prediction.

A new tool for identifying transient pockets on a protein surface, PSTP-finder, directly from trajectories of Molecular Dynamic simulations has been developed. An experimental procedure to validate the occurrence of transient pockets predicted by PSTP-finder, based on Nuclear Magnetic Resonance accessibility profiling of a paramagnetic probe on protein backbone amide hydrogens is also proposed. Sso7d, a chromatin protein of 62 residues from the hyperthermophilic archaeabacterium Sulfolobus solfataricus, has been used to test PSTP-finder and the NMR based validation procedure

Hot spot mapping of protein surfaces with TEMPOL: Bovine pancreatic RNase A as a model system

TEMPOL spin-label has been used to identify surface exposure of protein nuclei from NMR analysis of the induced paramagnetic relaxation enhancements (PRE). The absence of linear dependence between atom depths and observed PRE reveals that specific mechanisms drive the approach of the paramagnet to the protein surface. RNase A represents a unique protein system to explore the fine details of the information offered by TEMPOL induced PRE, due to the abundance of previous results, obtained in solution and in the crystal, dealing with surface dynamics behavior of this protein. MD simulations in explicit solvent have been performed, also in the presence of TEMPOL, in order to delineate the role of intermolecular hydrogen bonds (HB) on PRE extents. Comparison of our results with the ones obtained from multiple solvent crystal structure (MSCS) studies yields information on the specificities that these two techniques have for characterizing protein-ligand interactions, a fundamental step in the development of reliable surface druggability predictors

Searching for protein binding sites from Molecular Dynamics simulations and paramagnetic fragment-based NMR studies.

Hotspot delineation on protein surfaces represents a fundamental step for targeting protein-protein interfaces. Disruptors of protein-protein interactions can be designed provided that the sterical features of binding pockets, including the transient ones, can be defined. Molecular Dynamics, MD, simulations have been used as a reliable framework for identifying transient pocket openings on the protein surface. Accessible surface area and intramolecular H-bond involvement of protein backbone amides are proposed as descriptors for characterizing binding pocket occurrence and evolution along MD trajectories. TEMPOL induced paramagnetic perturbations on 1H- 15N HSQC signals of protein backbone amides have been analyzed as a fragment-based search for surface hotspots, in order to validate MD predicted pockets. This procedure has been applied to CXCL12, a small chemokine responsible for tumor progression and proliferation. From combined analysis of MD data and paramagnetic profiles, two CXCL12 sites suitable for the binding of small molecules were identified. One of these sites is the already well characterized CXCL12 region involved in the binding to CXCR4 receptor. The other one is a transient pocket predicted by Molecular Dynamics simulations, which could not be observed from static analysis of CXCL12 PDB structures. The present results indicate how TEMPOL, instrumental in identifying this transient pocket, can be a powerful tool to delineate minor conformations which can be highly relevant in dynamic discovery of antitumoral drugs

Dieci domande sulla riforma costituzionale

Analisi del procedimento di revisione della parte seconda della Costituzione e della natura del referendum previsto dall'art. 138 Cost

Dieci domande sulla riforma costituzionale

Discussione di alcuni nodi critici della riforma costituzionale della XVII legislatura, entro un Forum tra costituzionalisti invitati dalla redazione, muovendo da una serie di domande comuni proposte dalla rivista (gli invitati potevano scegliere liberamente se rispondere, in breve, a ciascuna di esse oppure dilungarsi di più su un numero ristretto di questioni)