Probing protein stability: towards a computational atomistic, reliable, affordable, and improvable model.

We present an improved application of a recently proposed computational method designed to evaluate the change of free energy as a function of the average value of a suitably chosen collective variable in proteins. The method is based on a full atomistic description of the protein and its environment. The goal is to understand how the protein melting temperature changes upon single-point mutations, because the sign of the temperature variation will allow us to discriminate stabilizing vs. destabilizing mutations in protein sequences. In this refined application the method is based on altruistic well-tempered metadynamics, a variant of multiple-walkers metadynamics. The resulting metastatistics is then modulated by the maximal constrained entropy principle. The latter turns out to be especially helpful in free-energy calculations as it is able to alleviate the severe limitations of metadynamics in properly sampling folded and unfolded configurations. In this work we apply the computational strategy outlined above in the case of the bovine pancreatic trypsin inhibitor, a well-studied small protein, which is a reference for computer simulations since decades. We compute the variation of the melting temperature characterizing the folding-unfolding process between the wild-type protein and two of its single-point mutations that are seen to have opposite effect on the free energy changes. The same approach is used for free energy difference calculations between a truncated form of frataxin and a set of five of its variants. Simulation data are compared to in vitro experiments. In all cases the sign of the change of melting temperature is reproduced, under the further approximation of using an empirical effective mean-field to average out protein-solvent interactions.

Quantum Coherence in Loopless Superconductive Networks.

Measurements indicating that planar networks of superconductive islands connected by Josephson junctions display long-range quantum coherence are reported. The networks consist of superconducting islands connected by Josephson junctions and have a tree-like topological structure containing no loops. Enhancements of superconductive gaps over specific branches of the networks and sharp increases in pair currents are the main signatures of the coherent states. In order to unambiguously attribute the observed effects to branches being embedded in the networks, comparisons with geometrically equivalent-but isolated-counterparts are reported. Tuning the Josephson coupling energy by an external magnetic field generates increases in the Josephson currents, along the above-mentioned specific branches, which follow a functional dependence typical of phase transitions. Results are presented for double comb and star geometry networks, and in both cases, the observed effects provide positive quantitative evidence of the predictions of existing theoretical models.

Prioritizing the First Doses of SARS-CoV-2 Vaccine to Save the Elderly: The Case Study of Italy.

SARS-CoV-2 is currently causing hundreds of deaths every day in European countries, mostly in not yet vaccinated elderly. Vaccine shortage poses relevant challenges to health authorities, called to act promptly with a scarcity of data. We modeled the mortality reduction of the elderly according to a schedule of mRNA SARS-CoV-2 vaccine that prioritized first dose administration. For the case study of Italy, we show an increase in protected individuals up to 53.4% and a decrease in deaths up to 19.8% in the cohort of over 80's compared with the standard vaccine recalls after 3 or 4 weeks. This model supports the adoption of vaccination campaigns that prioritize the administration of the first doses in the elderly.

Josephson Currents and Gap Enhancement in Graph Arrays of Superconductive Islands.

Evidence is reported that topological effects in graph-shaped arrays of superconducting islands can condition superconducting energy gap and transition temperature. The carriers giving rise to the new phase are couples of electrons (Cooper pairs) which, in the superconducting state, behave as predicted for bosons in our structures. The presented results have been obtained both on star and double comb-shaped arrays and the coupling between the islands is provided by Josephson junctions whose potential can be tuned by external magnetic field or temperature. Our peculiar technique for probing distribution on the islands is such that the hopping of bosons between the different islands occurs because their thermal energy is of the same order of the Josephson coupling energy between the islands. Both for star and double comb graph topologies the results are in qualitative and quantitative agreement with theoretical predictions.

Nonequilibrium transient phenomena in the washboard potential.

Transient properties of the one-dimensional washboard potential are investigated in order to understand observed modulations in the statistics of escape events. Specifically, we analyze the effects of different kinds of initial conditions on the escape distribution obtained by linearly increasing the tilt of the potential. Despite the complexity of the dynamics leading up to the eventual escape, we find that the overall statistics can be interpreted in terms of the system parameters, which offers illuminating perspectives for driven one-dimensional systems with washboard potentials. We choose parameters sets relevant for Josephson junctions, a commonly studied system due to both its applications and its use as a model system in condensed matter physics.