Giancarlo Rossi

Instantons and Supersymmetry

The role of instantons in describing non-perturbative aspects of globally supersymmetric gauge theories is reviewed. The cases of theories with N = 1, N = 2 and N = 4 supersymmetry are discussed. Special attention is devoted to the intriguing relation between instanton solutions in field theory and branes in string theory.

A first-principle calculation of the XANES spectrum of Cu2+ in water

The progress in high performance computing we are witnessing today offers the possibility of accurate electron density calculations of systems in realistic physico-chemical conditions. In this paper, we present a strategy aimed at performing a first-principle computation of the low energy part of the X-ray Absorption Spectroscopy (XAS) spectrum based on the density functional theory calculation of the electronic potential. To test its effectiveness, we apply the method to the computation of the X-ray absorption near edge structure part of the XAS spectrum in the paradigmatic, but simple case of Cu(2+) in water. In order to keep into account the effect of the metal site structure fluctuations in determining the experimental signal, the theoretical spectrum is evaluated as the average over the computed spectra of a statistically significant number of simulated metal site configurations. The comparison of experimental data with theoretical calculations suggests that Cu(2+) lives preferentially in a square-pyramidal geometry. The remarkable success of this approach in the interpretation of XAS data makes us optimistic about the possibility of extending the computational strategy we have outlined to the more interesting case of molecules of biological relevance bound to transition metal ions.

Studying the Cu binding sites in the PrP N-terminal region: a test case for ab initio simulations.

First principle ab initio molecular dynamics simulations of the Car–Parrinello type have proved to be of invaluable help in understanding the microscopic mechanisms of chemical bonding both in solid state physics and in structural biophysics. In this work we present as a test case a study of the Cu coordination mode at the Prion Protein binding sites localized in the N-terminal octarepeat region. Using medium size PC-clusters, we are able to deal with systems with up to about 350 atoms and 103 electrons for as long as ∼2 ps. With a foreseeable forthcoming scaling up of the available CPU times by a factor 103, one can hope to be soon able to simulate systems of biological interest of realistic size and for physical times of the order of the nanosecond

Molecular dynamics with the massively parallel APE computers

In this paper we discuss the general question of the portability of Molecular Dynamics codes for diffusive systems (liquids) on parallel computers of the APE family. The intrinsic single precision arithmetics of the today available APE platforms does not seem to affect the numerical accuracy of the simulations, while the absence of integer addressing from the CPU to individual nodes puts strong constraints on the possible programming strategies. As a test case, we report the results of the simulation of the dynamics of 512 molecules of liquid butane (C4H10) ta room temperature. After 30 to 50 ps of equilibrium, the system was followed along four long trajectories, each one more than 1.3 ns. The effective CPU time corresponding to the simulation of a trajectory of 1 ns on the Torre (512 nodes ≈ 25 Gigaflops) was ≈ 50 hours. The CPU time can be substantially reduced (by almost a factor 3), if the APE-assembler micro-code of the most time-consuming part of the program is carefully optimized.

Copper–zinc cross-modulation in prion protein binding

In this paper we report a systematic XAS study of a set of samples in which Cu(II) was progressively added to complexes in which Zn(II) was bound to the tetra-octarepeat portion of the prion protein. This work extends previous EPR and XAS analysis in which, in contrast, the effect of adding Zn(II) to Cu(II)–tetra-octarepeat complexes was investigated. Detailed structural analysis of the XAS spectra taken at both the Cu and Zn K-edge when the two metals are present at different relative concentrations revealed that Zn(II) and Cu(II) ions compete for binding to the tetra-octarepeat peptide by cross-regulating their relative binding modes. We show that the specific metal–peptide coordination mode depends not only, as expected, on the relative metal concentrations, but also on whether Zn(II) or Cu(II) was first bound to the peptide. In particular, it seems that the Zn(II) binding mode in the absence of Cu(II) is able to promote the formation of small peptide clusters in which triplets of tetra-octarepeats are bridged by pairs of Zn ions. When Cu(II) is added, it starts competing with Zn(II) for binding, disrupting the existing peptide cluster arrangement, despite the fact that Cu(II) is unable to completely displace Zn(II). These results may have a bearing on our understanding of peptide-aggregation processes and, with the delicate cross-regulation balancing we have revealed, seem to suggest the existence of an interesting, finely tuned interplay among metal ions affecting protein binding, capable of providing a mechanism for regulation of metal concentration in cells.

Parallel computing and molecular dynamics of biological membranes

Abstract In this talk I discuss the general question of the portability of Molecular Dynamics codes for diffusive systems on parallel computers of the APE family. The intrinsic single precision of the today available platforms does not seem to affect the numerical accuracy of the simulations, while the absence of integer addressing from CPU to individual nodes puts strong constraints on possible programming strategies. Liquids can be satisfactorily simulated using the “systolic” method. For more complex systems, like the biological ones at which we are ultimately interested in, the “domain decomposition” approach is best suited to beat the quadratic growth of the inter-molecular computational time with the number of atoms of the system. The promising perspectives of using this strategy for extensive simulations of lipid bilayers are briefly reviewed.

A simple atomistic model for the simulation of the gel phase of lipid bilayers

Abstract:In this paper we present the results of a large-scale numerical investigation of structural properties of a model of cell membrane, simulated as a bilayer of flexible molecules in vacuum. The study was performed by carrying out extensive Molecular Dynamics simulations, in the (NVE) micro-canonical ensemble, of two systems of different sizes ( 2×32 and 2×256 molecules), over a fairly large set of temperatures and densities, using parallel platforms and more standard serial computers. Depending on the dimension of the system, the dynamics was followed for physical times that go from few hundred picoseconds for the largest system to 5-10 nanoseconds for the smallest one. We find that the bilayer remains stable even in the absence of water and neglecting Coulomb interactions in the whole range of temperatures and densities we have investigated. The extension of the region of physical parameters that we have explored has allowed us to study significant points in the phase diagram of the bilayer and to expose marked structural changes as density and temperature are varied, which are interpreted as the system passing from a crystal to a gel phase.

Designing effective anticancer-radiopeptides. A Molecular Dynamics study of their interaction with model tumor and healthy cell membranes

One of the greatest merit of the use of radiopeptides in oncology is their selectivity which, however, brings about the drawback that each radiopeptide is specific for a given tumor type. To overcome this problem the direction currently taken in drug design is that of radiolabelling peptide hormones (or their analogues), relying on their intrinsic ability to bind to specific receptors in precise areas of the human body, at the cost, however, of a poor selectivity against healthy cells. We present here an extensive Molecular Dynamics study of a promising alternative inspired by the mechanism through which antimicrobial peptides interact with the negatively charged bacterial membranes. Appropriately modifying the human antimicrobial peptide, LL-37, we designed a functionalized radionuclide carrier capable of binding more strongly to the negatively charged (model) tumor membranes than to the neutral healthy ones. The mechanism behind this behaviour relies on the fact that at the slight acidic pH surrounding tumor tissues the histidines belonging to the peptide get protonated thus making it positively charged. We have investigated by an extended numerical study the way in which this artificial peptide interacts with models of tumor and healthy cell membranes, proving by Potential Mean Force calculations that the affinity of the peptide to model tumor membranes is significantly larger than to healthy ones. These features (high affinity and generic tumor selectivity) recommend antimicrobial derived customized carriers as promising theranostic constructs in cancer diagnostic and therapy.

TUNING FORCE-FIELD PARAMETERS BY PRESSURE MEASUREMENTS IN MICRO-CANONICAL SIMULATIONS

We show that the dramatic dependence of pressure on the parameters of the inter-molecular potential can be exploited to tune them to their best values. We support the viability of this strategy by a careful study of a fully diffusive Lennard–Jones fluid, showing that Lennard–Jones parameters can be easily optimized to better than a 1% accuracy.