Ricerc@Sapienza

The structural modifications induced on a 0.5 M Zn2+ aqueous solution by increasing the pressure to 6.4 GPa were investigated using a combination of X-ray absorption near edge structure (XANES) spectroscopy and molecular dynamics (MD) simulations. The Zn K-edge XANES experimental spectra show two different trends depending on the pressure and temperature conditions of the system. On the one hand, when the pressure is increased to 1.0 GPa while keeping the temperature at 300 K, the highly structured nature of Zn2+ second hydration shell is preserved.

Molecular dynamics (MD) simulations recently proved to be a useful tool for unveiling many aspects of pore formation in lipid membranes under the influence of external electric fields. In particular, the study of the structure and transport properties of electropores must definitely take advantage of a rigorous characterization of pore geometry and its evolution in time. In order to compare sizerelated properties of pores in bilayers of various compositions, generated and maintained under different physical and chemical conditions, reference metrics are needed.

Molecular dynamics (MD) simulations have proved to be a useful tool for unveiling many aspects of pore formation in lipid membranes under the influence of external electric fields. In order to compare the size-related properties of pores in bilayers of various compositions, generated and maintained under different physical and chemical conditions, reference metrics are needed for characterizing pore geometry and its evolution over time.

Recent papers showed that when dealing with nanosecond pulsed electric fields (nsPEFs), bipolar pulses proved far less effective at membrane permeabilization and at cell killing than monopolar ones, contrary to what happens in the microsecond range. The mechanism at the basis of such selective response of cells is not fully elucidated. One hypothesis worthwhile to test could be a direct action of nsPEFs on intracellular enzyme reactions.

We present here a new method for calculating the radius of a transmembrane pore in a phospholipid bilayer. To compare size-related properties of pores in bilayers of various compositions, generated and maintained under different physical and chemical conditions, reference metrics are needed. Operational metrics can be associated with some observed behavior. For example, pore size can be defined by the largest object that will pass through the length of the pore.

Intense pulsed electric fields are known to act at the cell membrane level and are already being exploited in biomedical and biotechnological applications. However, it is not clear if electric pulses within biomedically-attainable parameters could directly influence intra-cellular components such as cytoskeletal proteins. If so, a molecular mechanism of action could be uncovered for therapeutic applications of such electric fields.

The exchange proteins activated by cAMP (EPAC) are implicated in a large variety of physiological processes and they are considered as promising targets for a wide range of therapeutic applications. Several recent reports provided evidence for the therapeutic effectiveness of the inhibiting EPAC1 activity cardiac diseases. In that context, we recently characterized a selective EPAC1 antagonist named AM-001. This compound was featured by a non-competitive mechanism of action but the localization of its allosteric site to EPAC1 structure has yet to be investigated.

Commercially available pesticides were examined as Mus musculus and Homo sapiens acetylcholinesterase (mAChE and hAChE) inhibitors by means of ligand-based (LB) and structure-based (SB) in silico approaches. Initially, the crystal structures of simazine, monocrotophos, dimethoate, and acetamiprid were reproduced using various force fields. Subsequently, LB alignment rules were assessed and applied to determine the inter synaptic conformations of atrazine, propazine, carbofuran, carbaryl, tebufenozide, imidacloprid, diuron, monuron, and linuron.