M. Pintore

The binding mechanism of urea, hydroxamic acid and N-(N-butyl)-phosphoric triamide to the urease active site. A comparative molecular dynamics study

Abstract Molecular dynamics (MD) calculations have been performed on the active site of urease from Klebsiella aerogenes and its adducts with urea, hydroxamic acid and N -( n -butyl)-phosphoric triamide (NBPT). The catalytic nickel atoms were explicitly included in all the simulations. The nickel atoms, as shown by X-ray analysis, are linked by a carbamate bridge. Average MD structures were calculated starting from the X-ray structure of the urease active site and docking the ligand and the inhibitors from different starting conformations. The urea molecule binds to only one of the Ni atoms, the hydroxamic acid behaves like a monodentate or a bidentate ligand depending on the pH, and NBPT coordinates both the Ni centers and a carbamate residue via the formation of and hydrogen bond thus acting as a tridentate ligand. The proposed binding mechanisms agree with known data about hydroxamic and urea complexes with urease.

INTERACTION OF CA2+ AND NA+ IONS WITH POLYGALACTURONATE CHAINS : A MOLECULAR DYNAMICS STUDY

Partially esterified polygalacturonic acid is the main component of pectin in higher plants. The carboxylic groups and their methyl esters markedly affect the ability of the pectin molecules to bind oppositely charged ions and to form gels. In order to make a contribution to the understanding of the mechanisms which regulate the ionic transfer at the soil–root interface and in the apoplast, we report the results of a set of molecular dynamics experiments in which the interactions of four fully deprotonated fragments of polygalacturonic acid, each counting 12 units, 300 water molecules and 48 or 24 Na+ and Ca2+ ions were studied.We observed the formation of Ca2+ bridges between the polygalacturonate chains. The forces driving the aggregation processes are characterized by the formation of strong coulombic interactions between the metal ions and the carboxylate groups. The results are consistent with experiment evidence of the formation of Ca–polygalacturonate organized gels. The Ca–polygalacturonate complex exhibits a lower energy compared to that of Na–polygalacturonate. The ratio of the Na+ and Ca2+ diffusion coefficients agree well with experimental reports.

A molecular dynamics investigation on the occurrence of helices in polygalacturonic acid

Abstract Partially esterified polygalacturonic acid is the main component of pectin in higher plants. It constitutes the mucilaginous soil–root interface and acts as an accumulation phase for nutrients, being an important media for the diffusion of ions towards the root absorbing cells. The carboxylic groups and their methyl esters markedly affect the ability of the pectin molecules to bind oppositely charged ions and to form gels. Molecular Dynamics was employed to investigate the conformational equilibrium and the intermolecular interactions of a system constituted by two polygalacturonic acid chains, each formed by 24 units of galacturonic acid. The results suggest that, as evidenced for other polysaccharides, a helix based structure could be proposed for the polygalacturonic acid chains.

Molecular dynamics study of polygalacturonic acid chains in aqueous solution

Abstract Molecular dynamics (MD) simulations were performed on a system consisting of polygalacturonic acid (PGA) chains. MD experiments were conducted both in vacuo and in the presence of water. The PGA chains were formed by 12 GalA units and each chain had a molecular weight of 2132. Three chains were enclosed in the simulation cells. NPT runs, carried out either in the absence and in the presence of water molecules, evidenced the collapse of the chains which aggregate due to the formation of hydrogen bonds. NVT trajectories performed in the presence of water molecules show that the solvent moves in channels which separate the PGA aggregates. These findings well agree with experimental results about gel formation by PGA and other pectins in strong acid media.

A molecular modeling study on the interaction between β-cyclodextrin and synthetic pyretroids

Abstract The interaction between four cycloprothrin derivatives and β-cyclodextrin was investigated by means of molecular dynamics. Several in vacuo trajectories were calculated for each system imposing a 1:1 stoichiometry. Moreover, for one particular guest-host couple, the 1:2 guest-host ratio was investigated. We also took into account the influence of the solvent and of the temperature. The results account for the formation of adducts which are stable at room temperature. The formation of the adduct involves the phenyl groups of the guest molecules which mainly interact with the hydrophobic cavity of the host by van der Waals forces.

SIMULATIONS OF INTERLAYER METHANOL IN Ca- AND Na-SATURATED MONTMORILLONITES USING MOLECULAR DYNAMICS

Molecular dynamics computer simulations were used to study methanol molecules confined between the layers of 2:1 phyllosilicates. The model systems are based on natural Ca- and Na-rich montmorillonites. Data from the literature and determined by fitting the calculated layer spacing to experimental values were employed to obtain interactions between the charged 2:1 layers and the solvent molecules. The montmorillonite surface atoms were held rigid and the methyl group in the methanol molecule was represented by a soft Lennard-Jones sphere. Electrostatic interactions were determined by the Ewald sum method, whereas the van der Waals interactions were described by a Lennard-Jones potential. Comparison of our results with diffraction data indicates a good reproduction of the layer spacing. After the initial solvent layer forms, additional solvent layers form only after previous layers are complete. Each Ca2+ and Na+ ion in the monolayer has four and two methanol molecules, respectively, in the first solvation shell, whereas the solvation shell in the multilayer contains six and four methanol molecules, respectively. This agrees well with experimental data.

A molecular dynamics investigation on the inclusion of chiral agrochemical molecules in β-cyclodextrin. Complexes with dichlorprop, 2-phenoxypropionic acid and dioxabenzofos

Cyclodextrins are a group of cyclic oligosaccharides with a ring, basket-like structure. These compounds are able to include several kinds of molecules into their internal cavity, leading to important modifications of the properties of the guest compound. The interaction between β-cyclodextrin and the R and S enantiomers of dichlorprop, 2-phenoxypropionic acid and dioxabenzofos was investigated by means of molecular dynamics (MD). Several in vacuo trajectories were calculated for each system imposing a 1:1 stoichiometry. The results account for the formation of adducts which are stable at room temperature. The analysis of statistical data from the MD runs shows that dioxabenzofos exhibits the weakest interaction in the series studied and that the R and S enantiomers of dichlorprop and phenoxypropionic acid interact in a different fashion with the host molecule.

A molecular modeling study of the urease active site

Abstract Urease catalyzes the decomposition of urea to ammonium and carbamate ions by its active site which contains two nickel(II) atoms. Here we report the results of a molecular dynamics investigation performed on a system constituted of the cavity of the enzyme and one hydroxamic acid molecule which acts as an inhibitor of the protein. The results agree with experimental data and represent a valid starting point for the design of more efficient urease inhibitors.

A molecular modelling study of the interaction between beta-cyclodextrin and the organophosphorothioate pesticide parathion

The interaction between parathion and β-cyclodextrin was investigated by Molecular Dynamics. Several in vacuo trajectories were calculated for the system imposing a 1:1 stoichiometry. The influence of the solvent and temperature was considered. The results account for the formation of adducts which are stable at room temperature and involve mainly the nitrophenoxy group of the guest molecules which interacts with the hydrophobic cavity of the host by van der Waals forces.

A molecular dynamics study of the inclusion of monoand disubstituted benzenes in β-cyclodextrin

Abstract The interaction between β-cyclodextrin and five monoand disubstituted benzenes in water was investigated by means of molecular dynamics. The trajectories were calculated for each system, imposing a 1:1 host-guest stoichiometry with 512 water molecules. Periodic boundaryconditions were adopted. The results account for the formation of stable adducts and the predicted geometry agrees with experimental circular dichroism data.