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Titolo: Virtual rheological experiments on linear alkane chains confined between titanium walls

Titolo: Atomistic molecular dynamics simulations of gas diffusion and solubility in rubbery amorphous hydrocarbon polymers

Titolo: Activity of dasatinib against L576P KIT mutant melanoma: Molecular, cellular, and clinical correlates
Abstract: Point mutations in the KIT receptor tyrosine kinase gene have recently been identified in mucosal, acral lentiginous, and chronically sun-damaged melanomas. We have identified the first human melanoma cell line with an endogenous L576P mutation, the most common KIT mutation in melanoma ( 30-40%). In vitro testing showed that the cell viability of the L576P mutant cell line was not reduced by imatinib, nilotinib, or sorafenib small molecule KIT inhibitors effective in nonmelanoma cells with other KIT mutations. However, the viability of the mutant cells was reduced by dasatinib at concentrations as low as 10 nM (P = 0.004). Molecular modeling studies found that the L576P mutation induces structural changes in KIT that reduce the affinity for imatinib (ΔΔGbind = −2.52 kcal/mol) but not for dasatinib (ΔΔGbind = +0.32 kcal/mol). Two metastatic melanoma patients with the L576P KIT mutation were treated with dasatinib, including one patient previously treated with imatinib. Both patients had marked reduction (>50%) and elimination of tumor F18-fluorodeoxyglucose (FDG)-avidity by positron emission tomography (PET) imaging after dasatinib treatment. These
data support the selective inhibitory effect of dasatinib against cells harboring the most common KIT mutation in melanoma, and thus has therapeutic implications for acrallentiginous, chronic sun-damaged, and mucosal melanomas.

Titolo: The Sigma Enigma:In Vitro/in SilicoSite-Directed Mutagenesis Studies Unveil σ1Receptor Ligand Binding
Abstract: The σ1 receptor is an integral membrane protein that shares no homology with other receptor systems, has no unequivocally identified natural ligands, but appears to play critical roles in a wide variety of cell functions. While the number of reports of the possible functions of the σ1 receptor is increasing, almost no information about the three-dimensional structure of the receptor and/or possible modes of interaction of the σ1 protein with its ligands have been described. Here we performed an in vitro/in silico investigation to analyze the molecular interactions of the σ1 receptor with its prototypical agonist (+)-pentazocine. Accordingly, 23 mutant σ1 isoforms were generated, and their interactions with (+)-pentazocine were determined experimentally. All direct and/or indirect effects exerted by the mutant residues on the receptor-agonist interactions were reproduced and rationalized in silico, thus shining new light on the three-dimensional structure of the σ1 receptor and its ligand binding site.

Titolo: Low Pressure Equilibrium Data for the Prediction of Solubility in Carbon Dioxide.

Titolo: A Differential Static Apparatus for the Investigation of the Infinite Diluted Region.

Titolo: Thiazole-based sigma-1 receptor ligands: Diversity by late-stage C-H arylation of thiazoles, structure affinity and selectivity relationships and molecular interactions
Abstract: Spirocyclic thiophene derivatives represent promising sigma-1 ligands with high sigma-1 affinity and selectivity over the sigma-2 subtype. In order to increase ligand efficiency, the thiophene ring was replaced bioisosterically by a thiazole ring and the pyran ring was opened. Late-stage diversification by regioselective C-H arylation of thiazoles 9a-c resulted in a set of 53 compounds with high diversity. This set of compounds was analyzed with respect to sigma-1 affinity, sigma-1/sigma-2 selectivity, lipophilicity (logD7.4), lipophilicity-corrected ligand efficiency (LELP) and molecular target interactions. The most promising candidates are the pyridyl substituted thiazole derivatives 33c and 34c possessing low nanomolar 1 affinity (Ki = 1.3 nM and 1.9 nM), high 1/2 selectivity (>1500-fold), low lipophilicity (logD7.4 = 1.8) and very good ligand efficiency (LELP = 5.5) indicating promising pharmacodynamics and pharmacokinetics. Molecular simulation studies including docking and deconvolution of the free binding energy into its major components led to reduced hydrophobic stabilization of the pyridyl derivatives 33c and 34c, which is compensated by lower desolvation energy.

Titolo: MoDeNa: Modeling of morphology Development of micro and Nano Structures

Titolo: Simple, Fast, and Accurate In silico Estimations of Contact Angle, Surface Tension, and Work of Adhesion of Water and Oil Nanodroplets on Amorphous Polypropylene Surfaces

Titolo: Nano tools for macro problems: multiscale molecular modeling of nanostrucured polymer systems