Elucidation of the disulfide folding pathway of hirudin by a topology-based approach

A theoretical model for the folding of proteins containing disulfide bonds is introduced. The model exploits the knowledge of the native state to favour the progressive establishment of native interactions. At variance with traditional approaches based on native topology, not all native bonds are treated in the same way; in particular, a suitable energy term is introduced to account for the special strength of disulfide bonds (irrespective of whether they are native or not) as well as their ability to undergo intra-molecular reshuffling. The model thus possesses the minimal ingredients necessary to investigated the much debated issue of whether the re-folding process occurs through partially structured intermediates with native or non-native disulfide bonds. This strategy is applied to a context of particular interest, the re-folding process of Hirudin, a thrombin-specific protease inhibitor, for which conflicting folding pathways have been proposed. We show that the only two parameters in the model (temperature and disulfide strength) can be tuned to reproduce well a set of experimental transitions between species with different number of formed disulfide. This model is then used to provide a characterisation of the folding process and a detailed description of the species involved in the rate-limiting step of Hirudin refolding.Comment: 14 pages, 9 figure

Model adaptation enriched with an anisotropic mesh spacing for nonlinear equations: application to environmental and CFD problems

Goal of this paper is to suitably combine a model with an anisotropic mesh adaptation for the numerical simulation of nonlinear advection-diffusion-reaction systems and incompressible flows in ecological and environmental applications. Using the reduced-basis method terminology, the proposed approach leads to a noticeable computational saving of the online phase with respect to the resolution of the reference model on nonadapted grids. The search of a suitable adapted model/mesh pair is to be meant, instead, in an offline fashion

Surface spin-flop phases and bulk discommensurations in antiferromagnets

Phase diagrams as a function of anisotropy D and magnetic field H are obtained for discommensurations and surface states for a model antiferromagnet in which $H$ is parallel to the easy axis. The surface spin-flop phase exists for all $D$. We show that there is a region where the penetration length of the surface spin-flop phase diverges. Introducing a discommensuration of even length then becomes preferable to reconstructing the surface. The results are used to clarify and correct previous studies in which discommensurations have been confused with genuine surface spin-flop states.Comment: 4 pages, RevTeX, 2 Postscript figure

Surface spin-flop and discommensuration transitions in antiferromagnets

Phase diagrams as a function of anisotropy $D$ and magnetic field $H$ are obtained for discommensurations and surface states for an antiferromagnet in which $H$ is parallel to the easy axis, by modeling it using the ground states of a one-dimensional chain of classical XY spins. A surface spin-flop phase exists for all $D$, but the interval in $H$ over which it is stable becomes extremely small as $D$ goes to zero. First-order transitions, separating different surface states and ending in critical points, exist inside the surface spin-flop region. They accumulate at a field $H'$ (depending on $D$) significantly less than the value $H_{SF}$ for a bulk spin-flop transition. For $H' < H < H_{SF}$ there is no surface spin-flop phase in the strict sense; instead, the surface restructures by, in effect, producing a discommensuration infinitely far away in the bulk. The results are used to explain in detail the phase transitions occurring in systems consisting of a finite, even number of layers.Comment: Revtex 17 pages, 15 figure

Shell and spatial structures: Between new developments and historical aspects

Advanced structural systems are more and more devoted to light, versatile, eco-sustainable structures. This goal can be achieved through the use of new materials and new approaches for structural optimization, form finding, design, and validation. Shell and spatial structures are representative of some of the most efficient structural systems in which the optimized use of materials is combined with effective structural forms and shapes. The ongoing development of analysis methods, design approaches and construction techniques of shell and spatial structures has resulted in an increasing interest from engineers, architects, and builders. This Special Issue is devoted to papers coming from a call principally addressed to the participants of the 1st Italian Workshop on Shell and Spatial Structures (https://sites.google.com/view/iwss2020/home) held online the last June 2020 after the lockdown restriction due to the Covid-19 pandemic (Figure 1). The experience of the first IWSS (IWSS2020) was particularly innovative. It brought together the interests of the Italian and the international community devoted to the study and applications of shell and spatial structures. The IWSS received two significant endorsements, from the IASS (www.iassstructures.org) and from the SISCO (www. siscoscienzadellecostruzioni.org)

Anharmonicity and self-similarity of the free energy landscape of protein G

The near-native free energy landscape of protein G is investigated through 0.4 microseconds-long atomistic molecular dynamics simulations in explicit solvent. A theoretical and computational framework is used to assess the time-dependence of salient thermodynamical features. While the quasi-harmonic character of the free energy is found to degrade in a few ns, the slow modes display a very mild dependence on the trajectory duration. This property originates from a striking self-similarity of the free energy landscape embodied by the consistency of the principal directions of the local minima, where the system dwells for several ns, and of the virtual jumps connecting them.Comment: revtex, 6 pages, 5 figure

Continuum model for polymers with finite thickness

We consider the continuum limit of a recently-introduced model for discretized thick polymers, or tubes. We address both analytically and numerically how the polymer thickness influences the decay of tangent-tangent correlations and find how the persistence length scales with the thickness and the torsional rigidity of the tube centerline. At variance with the worm-like chain model, the phase diagram that we obtain for a continuous tube is richer; in particular, for a given polymer thickness there exists a threshold value for the centerline torsional rigidity separating a simple exponential decay of the tangent-tangent correlation from an oscillatory one.Comment: 8 pages, 4 figures. Accepted for publication in J. Phys.

Thiourea Derivative of 2-[(1 R)-1-Aminoethyl]phenol: A Flexible Pocket-like Chiral Solvating Agent (CSA) for the Enantiodifferentiation of Amino Acid Derivatives by NMR Spectroscopy

Thiourea derivatives of 2-[(1R)-1-aminoethyl]phenol, (1S,2R)-1-amino-2,3-dihydro-1H-inden-2-ol, (1R,2R)-(1S,2R)-1-amino-2,3-dihydro-1H-inden-2-ol, and (R)-1-phenylethanamine have been compared as chiral solvating agents (CSAs) for the enantiodiscrimination of derivatized amino acids using nuclear magnetic resonance (NMR) spectroscopy. Thiourea derivative, prepared by reacting 2-[(1R)-1-aminoethyl]phenol with benzoyl isothiocyanate, constitutes an effective CSA for the enantiodiscrimination of N-3,5-dinitrobenzoyl (DNB) derivatives of amino acids with free or derivatized carboxyl functions. A base additive 1,4-diazabicyclo[2.2.2]octane(DABCO)/N,N-dimethylpyridin-4-amine (DMAP)/NBu4OH) is required both to solubilize amino acid derivatives with free carboxyl groups in CDCl3 and to mediate their interaction with the chiral auxiliary to attain efficient differentiation of the NMR signals of enantiomeric substrates. For ternary systems CSA/substrate/DABCO, the chiral discrimination mechanism has been ascertained through the NMR determination of complexation stoichiometry, association constants, and stereochemical features of the diastereomeric solvates