Gilberto Giugliarelli

The solubility and compactness of proteins is investigated within the framework of models amenable to an exact numerical study through exhaustive enumeration. We study how the average inter-amino acid interaction potential affects the properties of both isolated and interacting proteins. In a concentrated solution, depending on the value of the average potential, individual proteins may remain stable in the isolated native structure (soluble case), may aggregate preserving their geometrical shape (nonsoluble case) or aggregate changing their geometrical shape (prionlike behavior). The number of sequences that have compact native states and are soluble is maximal at a fine-tuned average interaction potential and of the same order of the corresponding number of nonsoluble prionlike proteins. The viable protein sequences selected by such a fine-tuned potential are found to have an amino acid composition similar to naturally occurring proteins.

Reduced representations of proteins have been playing a keyrole in the study of protein folding. Many such models are available, with different representation detail. Although the usefulness of many such models for structural bioinformatics applications has been demonstrated in recent years, there are few intermediate resolution models endowed with an energy model capable, for instance, of detecting native or native-like structures among decoy sets. The aim of the present work is to provide a discrete empirical potential for a reduced protein model termed here PC2CA, because it employs a PseudoCovalent structure with only 2 Centers of interactions per Amino acid, suitable for protein model quality assessment.All protein structures in the set top500H have been converted in reduced form. The distribution of pseudobonds, pseudoangle, pseudodihedrals and distances between centers of interactions have been converted into potentials of mean force. A suitable reference distribution has been defined for non-bonded interactions which takes into account excluded volume effects and protein finite size. The correlation between adjacent main chain pseudodihedrals has been converted in an additional energetic term which is able to account for cooperative effects in secondary structure elements. Local energy surface exploration is performed in order to increase the robustness of the energy function.The model and the energy definition proposed have been tested on all the multiple decoys' sets in the Decoys'R'us database. The energetic model is able to recognize, for almost all sets, native-like structures (RMSD less than 2.0 A). These results and those obtained in the blind CASP7 quality assessment experiment suggest that the model compares well with scoring potentials with finer granularity and could be useful for fast exploration of conformational space. Parameters are available at the url: http://www.dstb.uniud.it/~ffogolari/download/.

Electron spin relaxation rates over the temperatue range 1.41-15.6 K are presented for the copper-containing protein plastocyanin. Measurements are described for two samples, each derived from a different preparation of equivalent purity, for which the ionic, redox, and protein compositions varied slightly. X-band data are analyzed in terms of a phonon-limited direct process and a Raman relaxation process, where the index of the Raman transport integral is treated as a fitting parameter. Both samples yield rate data at the highest temperatures that are characterized by small deviations from a simple T(n) power law dependence, with n in the range 4.8-5.2. These deviations are most easily quantified when the T(n) power law fits are compared with similar functions that allow for a finite cutoff in the phonon density of states corresponding to Debye temperatures between 90 and 100 K with n in the range 5.0-5.5.

A theoretical method for EPR-spectra simulation of Cu2+ complexes in frozen aqueous solutions is presented. By assuming a gaussian distribution of the g# and A# spin-hamiltonian parameters, the method takes very satisfactorily into account both the increase in linewidth of the hyperfine lines in order of increasing m1 and the unequal spacing betwem the lines observed in experimental spectra and arising from strain effects during freezing.

A theoretical model for E.P.R. spectra simulation of Cu2+-complexes in frozen aqueous solutions is presented. By assuming a gaussian distribution of the g ‖ and A ‖ spin-hamiltonian parameters, the method takes very satisfactory account of both the increase in linewidth of the hyperfine lines in order of increasing m 1 and of the unequal spacing between these lines observed in experimental spectra that arises from strain effects during freezing. The model is expressed in a formalism derived from the frequency-swept domain and translated, for E.P.R. spectra synthesis, into the field-swept domain.

Depinning of an interface from a random self-affine substrate with roughness exponent ${\mathrm{\ensuremath{\zeta}}}_{\mathit{S}}$ is studied in systems with short-range interactions. In two dimensions transfer matrix results show that for ${\mathrm{\ensuremath{\zeta}}}_{\mathit{S}}$1/2 depinning falls in the universality class of the flat case. When ${\mathrm{\ensuremath{\zeta}}}_{\mathit{S}}$ exceeds the roughness (${\mathrm{\ensuremath{\zeta}}}_{0}$=1/2) of the interface in the bulk, geometrical disorder becomes relevant and, moreover, depinning becomes discontinuous. The same unexpected scenario, and a precise location of the associated tricritical point, are obtained for a simplified hierarchical model. It is inferred that, in three dimensions, with ${\mathrm{\ensuremath{\zeta}}}_{0}$=0, depinning turns first order already for ${\mathrm{\ensuremath{\zeta}}}_{\mathit{S}}$\ensuremath{\gtrsim}0. Thus critical wetting may be impossible to observe on rough substrates. \textcopyright{} 1996 The American Physical Society.

A lattice-gas model for physical adsorption of a gas on a fractal surface is solved in mean-field approximation. Adsorption isotherms display a rich structure with first and second order transitions. Surface tension and temperature effects are analysed. The possibility of determining the surface fractal dimension on the basis of "monolayer" adsorption measurements is discussed. Results for the multilayer adsorption regime are also presented and compared with recent scaling conjectures.

Transfer-matrix results in 2D show that wetting of a rough, self-affine wall induced by bulk bond disorder turns discontinuous as soon as the wall roughness exponent ζW exceeds ζ0 = 2/3, the spatial anisotropy index of interface fluctuations in the bulk. For ζW < 2/3 critical wetting is recovered, in the same universality class as for the flat-wall case. These and related findings suggest a free-energy structure such to imply first-order wetting also without disorder, or in 3D, whenever ζW exceeds the appropriate ζ0. The same thresholds should apply also with van der Waals forces, in cases when ζ0 implies a strong-fluctuation regime.

An inexpensive, versatile computer interface for a Varian E109 spectrometer has been realised. This interface, which is constructed using low cost and easily available electronic components, is able to communicate actively (listen and talk mode) with the host computer through the IEEE-488 standard bus. The hardware of the interface provides a means for: controlling the magnetic field without any manipulation of the spectrometer field controller; recording, in a digital form, the EPR analogue signal; and plotting any computer synthesised and/or stored spectrum on the EPR X-Y recorder. All the hardware diagrams and a summary of the data acquisition and processing software are presented.

ESR analysis conducted on frozen aqueous solutions of sodium hydroxide doped with 65Cu2+ ions showed the presence of g and A strain in the amorphous phase obtained by rapid cooling below 170 K. Upon heating above 205 K but keeping the temperature below the melting point the sample structure switched to a polycrystalline phase revealed by a complete release of the spectral strain. Evidence for a slightly different coupling of the copper electronic spin to the phonon bath is observed in the two phases.

A $2D$ model describing depinning of an interface from a rough, self-affine substrate, is studied by transfer matrix methods. The phase diagram is determined for several values of the roughness exponent, $\zeta_S$, of the attractive wall. For all $\zeta_S>0$ the following scenario is observed. In first place, in contrast to the case of a flat wall ($\zeta_S=0$), for wall attraction energies between zero and a $\zeta_S$-dependent positive value, the substrate is always wet. Furthermore, in a small range of attraction energies, a dewetting transition first occurs as T increases, followed by a wetting one. This unusual reentrance phenomenon seems to be a peculiar feature of self-affine roughness, and does not occur, e. g., for periodically corrugated substrates.

The interaction of copper ions with tRNA has been studied by optical and EPR spectroscopies. The interaction results in two different paramagnetic complexes characterized by a tetragonal symmetry of the ligand electric field sensed by the ions. The complete set of the spin Hamiltonian parameters has been extracted by computer simulation with the Monte Carlo method. Hypotheses concerning the putative ligands are put forward.

The first investigation of the spectral dimension of a deterministic fractal surface is presented. Somewhat unexpectedly, numerical results strongly suggest = 2 for a whole class of surfaces, enclosing space regions with ordinary volume dimension. This conclusion is also supported by scaling arguments based on a connection with processes of diffusion in the presence of hierarchical waiting times. The problem of diffusion on our surface is also compared with that of random chain conformations. Within the numerical uncertainties the two problems seem to be characterized by identical end-to-end distance exponents.

We study a $d=2$ discrete solid--on--solid model of complete wetting of a rough substrate with random self--affine boundary, having roughness exponent $\zeta_s$. A suitable transfer matrix approach allows to discuss adsorption isotherms, as well as geometrical and thermal fluctuations of the interface. For $\zeta_s\leq 1/2$ the same wetting exponent $\psi=1/3$ as for flat substrate is obtained for the dependence of the coverage, $\theta$, on the chemical potential, $h$ ($\theta\sim h^{-\psi}$ for $h\to 0$). The expected existence of a zero temperature fixed point, leading to $\psi=\zeta_s /(2-\zeta_s)$ for $\zeta_s>1/2$, is verified numerically in spite of an unexpected, very slow convergence to asymptotics.

Silicon Pixel detectors are at the core of the current and planned upgrade of the ATLAS experiment at LHC. They constitute the part of ATLAS closest to the interaction point and for this reason they will be exposed – over their lifetime – to a significant amount of radiation: prior to the HL-LHC, the innermost layers will receive a fluence of 1015neq∕cm2 and their HL-LHC upgrades will have to cope with an order of magnitude higher fluence integrated over their lifetimes. The paper presents a new digitization model that includes radiation damage effects for 3D Pixel sensors of the ATLAS Detector. The results of the calculation model concerning charge collection efficiency show a very good agreement with existing data in literature.

A computer interface for an EPR spectrometer is based on the IEEE 488 standard and is controlled by the HP86A.

Polymer adsorption on fractally rough walls of varying dimensionality is studied by renormalization group methods on hierarchical lattices. Exact results are obtained for deterministic walls. The adsorption transition is found continuous for low dimension dw of the adsorbing wall and the corresponding crossover exponent monotonically increases with dw, eventually overcoming previously conjectured bounds. For dw exceeding a threshold value dw*, becomes one and the transition changes to first order. dw*>dsaw, the fractal dimension of the polymer in the bulk. An accurate numerical approach to the same problem with random walls gives evidence of the same scenario.

The unbinding properties of an interface near structured wedges are investigated by discrete models with short range interactions. The calculations demonstrate that interface unbinding takes place in two stages: (i) a continuous fillinglike transition in the pure wedgelike parts of the structure, and (ii) a conclusive discontinuous unbinding. In 2D an exact transfer matrix approach allows us to extract the whole interface phase diagram and the precise mechanism at the basis of the phenomenon. The Metropolis Monte Carlo simulations performed in 3D reveal an analogous behavior. The emerging scenario allows us to shed new light onto the problem of wetting of geometrically rough walls.

A simple lattice protein model is used to study the effects of aggregation phenomena on protein folding. Folding kinetics of non‐isolated protein molecules is studied: different molecules can interact each other and, in competition with folding, aggregation (formation of a dimer) can occur. We consider two types of protein sequences for this analysis: a) very well designed sequences corresponding to very good folders (very small folding times); b) sequences which present kinetic partitioning in the folding kinetics. Kinetic partitioning mechanisms are due to structural intermediates in the folding path which generate alternative tracks (usually slower) to folding. Our study, developed by means of standard Monte Carlo approaches, shows that folding of sequences presenting kinetic partitioning are more likely to be affected by aggregation phenomena. These results are compared with the folding behavior of good folders and with misfolding and aggregation of prion‐like proteins.

Polymer adsorption on fractally rough walls of varying dimensionality is studied by renormalization group methods on hierarchical lattices. Exact results are obtained for deterministic walls. The adsorption transition is found continuous for low dimension $d_w$ of the adsorbing wall and the corresponding crossover exponent $ϕ$ monotonically increases with $d_w$, eventually overcoming previously conjectured bounds. For $d_w$ exceeding a threshold value $d_w^*$, $ϕ$ becomes 1 and the transition turns first--order. $d_w^*&gt;d_{saw}$, the fractal dimension of the polymer in the bulk. An accurate numerical approach to the same problem with random walls gives evidence of the same scenario.

Randomly oriented tetragonal complexes of copper ions (S=½) show in the low field region (g∥ region) of their Electron Paramagnetic Resonance (EPR) spectrum, four lines centered at g∥ and separated by An which arise from the hyperfine coupling to the copper nucleus (I=3/2). The width of these lines has been reported to exhibit a dependence on the nuclear quantum number, mI, of copper (1–4) and on the microwave frequency (1). Moreover we found the existence of an unequal spacing between the four parallel hyperfine lines, occurring to a variable extent from complex to complex (5). Such an effect was particularly evident in the EPR spectrum of the Cu++-tRNA complex where an appreciable shift of the mI=½ hyperfine lines was observed (6). To take into account the dependence of both the width and the resonant field position of the parallel hyperfine lines, we have recently developed a theoretical model for the simulation of the EPR spectra of copper complexes (5). The model, which assumes a Gaussian distribution of g∥ and A∥ values as due to strain occurring during freezing, has been successfully used to obtain the best fit of several X-band tetragonal copper spectra arising from complexes in the frozen state.