The Camerino symposium series (1978–2013): a privileged observatory of receptorology development

The organizers of the Camerino Receptor Symposia survey the development of receptorology. They trace the course from the first Symposium in 1978, which laid the foundation for Pirenzepine, the first selective muscarinic antagonist, to the 2010 Symposium, which highlighted the utility of functional simple domain antibodies (nanobodies) as novel G Protein-Coupled Receptor (GPCR) modulators. This 30-year period sees the acceptance of terms such as G-protein, auto- and heteroreceptors, site-directed mutagenesis, chimeric receptors, constitutive activity, inverse agonism, and orphan receptors. GPCRs are finally a reality and Langley and Ehrlich, if they returned to their laboratories, would be proud of how their intuitions have been realized

Overview on Radiolabel-Free in Vitro Assays for GPCRs

G-protein coupled receptors (GPCRs) represent important targets for drug discovery because they participate in a wide range of cellular signalling pathways that play a role in a variety of pathological conditions. The characterization of the patho-physiological profile and functional roles of new receptors is highly dependent on the availability of potent and selective ligands and new screening assays. The study of the pharmacological profile of new chemical entities is very important in order to predict the activity of drugs and their clinical adverse effect in humans. In the last decade, a large number of new in vitro radiolabel-free assays were developed and relevant information on diseases was upgraded. In particular, radiolabel-free assays led significant easy to handle and safer tools for operators. The aim of this review is to analyze these assays in terms of new drug activity and toxicology prediction and translation of non-clinical findings to humans in order to provide a powerful tool to aid drug development

Photoionization of furan from the ground and excited electronic states

Here we present a comparative computational study of the photoionization of furan from the ground and the two lowest-lying excited electronic states. The study aims to assess the quality of the computational methods currently employed for treating bound and continuum states in photoionization. For the ionization from the ground electronic state, we show that the Dyson orbital approach combined with an accurate solution of the continuum one particle wave functions in a multicenter B-spline basis, at the density functional theory (DFT) level, provides cross sections and asymmetry parameters in excellent agreement with experimental data. On the contrary, when the Dyson orbitals approach is combined with the Coulomb and orthogonalized Coulomb treatments of the continuum, the results are qualitatively different. In excited electronic states, three electronic structure methods, TDDFT, ADC(2), and CASSCF, have been used for the computation of the Dyson orbitals, while the continuum was treated at the B-spline/DFT level. We show that photoionization observables are sensitive probes of the nature of the excited states as well as of the quality of excited state wave functions. This paves the way for applications in more complex situations such as time resolved photoionization spectroscopy