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In this paper we report the description, implementation and application of a kinetic model designed for describing the Covid-19 epidemic spread in Italy and Germany in the period between February and June 2020 coinciding with the beginning of the statistical regime of the epidemic spread and the application of restrictive government measures aimed at its containment. The model, which makes use of a limited number of parameters, in spite of its simplicity is able of capturing the essential physical features of the epidemic spread highlighting the essential role of the restrictive measures and in particular the timeliness of their application for the containment of the most dramatic consequences. This work also confirms how the epidemic spread, if considered during its statistical-regime evolution, can be properly described - and hence probably better understood - using languages and methodologies typically adopted for chemical processes, such as the Mass Action Law and Chemical Kinetics.

International audience; A joint application of experimental and computational approaches has revealed the exceptionally high attitude of crabrolin, a 13-residue peptide with sequence FLPLILRKIVTAL-NH2, to adopt alpha-helix conformation not only in membrane-mimicking solvents but also in the presence of a not negligible amount of water. Our study shows that this propensity essentially resides in the intrinsic thermodynamic stability of alpha-helix conformation whose kinetic stability is drastically reduced in water solvent. Our analysis suggest that this is due to two effects enhanced by water; a more local effect consisting of the demolition of intra-peptide H-bonds, essential for the alpha-helix formation, and a bulk-electrostatic-effect favoring conformational states more polar than alpha-helix.

Time dependent density functional theory (TD-DFT) using different gradient-corrected density functionals, Becke's three-parameter hybrid method using the Lee–Yang–Parr correlation functional (B3LYP), Becke's exchange functional and Lee–Yang–Parr correlation functional (BLYP) and an hybrid DFT/HF approach based on the Perdew–Burke–Erzenrhof exchange-correlation functional (PBE1PBE), are applied to calculate vertical transitions from ground to the low-lying singlet electronic excited states of 1,2,3-triazine, in vacuum and in aqueous solution. Our results are in excellent agreement with a recent high resolution UV/VUV experimental work in the gas phase and with previous high level computational methods in vacuum and in solution. The results clearly show the potentialities of the combined TD-DFT/CPCM approach, within the gradient-corrected approximation (GGA), on aquo-complexes for the study of structural and spectroscopic properties in liquid phase.

The effect of cyclochirality of rccc-2,8,14,20-tetra-n-decyl-4,10,16,22-tetra-O-methylresorcin[4]arene (C) on the enantiodiscrimination of a number of chiral bidentate and tridentate aromatic and aliphatic biomolecules (G) has been investigated by nano-electrospray ionization (nano-ESI)-Fourier transform ion cyclotron resonance mass spectrometry. The experimental approach is based on the formation of diastereomeric proton-bound [C center dot H center dot G](+) complexes by nano-ESI of solutions containing an equimolar amount of quasi-enantiomers (C) together with the chiral guest (G) and the subsequent measurement of the rate of the G substitution by the attack of several achiral and chiral amines. In general, the heterochiral complexes react faster than the homochiral ones, except when G is an aminoalcoholic neurotransmitter whose complexes, beyond that, exhibit the highest enantioselectivity. The kinetic results were further supported by both collision-induced dissociation experiments on some of the relevant [C-2 center dot H center dot G](+) three-body species and Density functional theory (DFT) calculations performed on the most selective systems. Copyright (C) 2012 John Wiley & Sons, Ltd.

Quadratic configuration interaction procedure with single and double electronic excitations (QCISD) has been used, for the first time, to calculate the electronic structure of the Compound I (CpdI), which represents a key intermediate in the catalytic cycle of Horseradish Peroxidase (HRP) enzyme. The QCISD method is applied to lowest quasi-isoenergetic doublet and quartet spin multiplicity and results compared with density functional theory (DFT/B3LYP) data. This investigation shows that, at present, QCISD is more accurate than DFT-based approach in discriminating between the two lowest magnetic states of CpdI complex in HRP enzyme. Such a result opens the possibility of theoretically addressing the reaction mechanism leading to CpdI complex in HRP using a correlated wavefunction based approach. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010

Molecular dynamics simulations on hydrogen peroxide complex with wild-type (WT) and Arg38Leu mutated (R38L) Horseradish Peroxidase (HRP) were carried out over nanoseconds timescale in water solution at 300 K. Comparison of the results provides interesting insights about the role of highly conserved Arg38 and His42 residues in the chemical features of HRP, underlying its biological activity which initiates with Compound0 (Cpd0). In the WT-HRP enzyme current molecular dynamics simulations show, for the first time, that Arg38 residue: i) prevents the entrance of water inside the reaction cavity, hence providing a hydrophobic reactive scenario, ii) it maintains the distance between His42 and heme-H2O2 complex suitable for the occurrence of proton transfer reaction leading, thereafter, to heme-H2O2 disruption according to Poulos-Kraut mechanism. On the other hand, R38L mutant can be considered as a "wet enzyme" where the presence of water solvent molecules in the heme reaction pocket, unfavoring the initial heme-H2O2 complex formation, decreases the catalytic efficiency in agreement with experimental kinetics measurements. Furthermore, we note that Arg38Leu mutation pushes the His42 residue far from the heme-H2O2 complex, making unlikely a direct proton transfer and suggesting that, in the mutant, a solvent water molecule could be involved in the first step of the Poulos-Kraut mechanism.

Three novel peptidomimetic phosphinate inhibitors have been synthesized and evaluated as inhibitors of matrix metalloprotemases MMP-2 and MMP-8. Their IC50 values are in the micromolar range, and one of them showed to be the most effective inhibitor of MMP-2. The differences in binding affinities for MMP-2 and MMP-8 of the three phosphinates have been rationalized by means of modelling studies and molecular dynamics simulations

Glutamate synthase (GltS) is a complex iron-sulfur flavoprotein that catalyzes the reductive transfer of L-glutamine amide group to the C2 carbon of 2-oxoglutarate yielding two molecules of L-glutamate. Molecular dynamics calculations in explicit solvent were carried out to gain insight into the conformational flexibility of GltS and into the role played by the enzyme substrates in regulating the catalytic cycle. We have modelled the free (unliganded) form of Azospirillum brasilense GltS alpha subunit and the structure of the reduced enzyme in complex with the L-glutamine and 2-oxoglutarate substrates starting from the crystallographically determined coordinates of the GltS alpha subunit in complex with L-methionine sulphone and 2-oxoglutarate. The present 4-ns molecular dynamics calculations reveal that the GltS glutaminase site may exist in a catalytically inactive conformation unable to bind glutamine, and in a catalytically competent conformation, which is stabilized by the glutamine substrate. Substrates binding also induce (1) closure of the loop formed by residues 263-271 with partial shielding of the glutaminase site from solvent, and (2) widening of the ammonia tunnel entrance at the glutaminase end to allow for ammonia diffusion toward the synthase site. The Q-loop of glutamate synthase, which acts as an active site lid in other amidotransferases, seems to maintain an open conformation. Finally, binding of L-methionine sulfone, a glutamine analog that mimics the tetrahedral transient species occurring during its hydrolysis, causes a coordinated rigid-body motion of seaments of the glutaminase domain that results in the inactive conformation observed in the crystal structure of GltS alpha subunit.

Human neutrophil collagenase (HNC,MMP-8) is one of the target enzymes for drug treatment of pathologic extracellular matrix degradation. Peptidomimetic inhibitors bind in the S'-side of the enzyme active site occupying the S1' primary specificity pocket by their large hydrophobic side-chains. The crystal structure of the complex between the catalytic domain of MMP-8 and Pro-Leu-TrpP(OH)2 (PLTP) showed that this phosphonate inhibitor binds in the S side of the active site. This finding was unexpected since it represents the first example of accomodation of the bulky Trp indolyl chain in the S1 rather than in the S1' subsite. Dynamical and structural factors favouring this uncommon mode of binding were therefore investigated. Molecular dynamics (MD) simulations performed on the uncomplexed enzyme show that its structure in aqueous solution is only slightly different from the crystal structure found in the complex with PLTP. Essential dynamics analysis of the MD simulations, performed on PLTP alternatively interacting with the S- or S'-side of the active site, shows that the enzyme fluctuation increases in both cases. The main contribution to the overall enzyme fluctuation is given by the loop 164-173. The fluctuation of this loop is spread over more degrees of freedom when PLTP interacts with the S-side. This dynamical factor can enhance the preference of PLTP for the S subsites of MMP-8. MD simulations also show that ligation of PLTP in the S subsites is further favoured by better zinc chelation, a cation-p interaction at the S3 subsite and unstrained binding conformations. The role of the S3, S3' and S1' subsites in determining the inhibitor binding is dicussed.