Luiz Carlos Gomide Freitas

Interaction of the Disaccharide Trehalose with a Phospholipid Bilayer: A Molecular Dynamics Study

The disaccharide trehalose is well known for its bioprotective properties. Produced in large amounts during stress periods in the life of organisms able to survive potentially damaging conditions, trehalose plays its protective role by stabilizing biostructures such as proteins and lipid membranes. In this study, molecular dynamics simulations are used to investigate the interaction of trehalose with a phospholipid bilayer at atomistic resolution. Simulations of the bilayer in the absence and in the presence of trehalose at two different concentrations (1 or 2 molal) are carried out at 325 K and 475 K. The results show that trehalose is able to minimize the disruptive effect of the elevated temperature and stabilize the bilayer structure. At both temperature, trehalose is found to interact directly with the bilayer through hydrogen bonds. However, the water molecules at the bilayer surface are not completely replaced. At high temperature, the protective effect of trehalose is correlated with a significant increase in the number of trehalose-bilayer hydrogen bonds, predominantly through an increase in the number of trehalose molecules bridging three or more lipid molecules.

Rotational features of carbon-nitrogen bonds in axially chiral o-tert-butyl anilides and related molecules. Potential substrates for the ‘prochiral auxiliary’ approach to asymmetric synthesis

Abstract A new strategy for asymmetric induction termed the ‘prochiral auxiliary’ approach is introduced. Reactions of acylating agents with prochiral N -methyl- o - tert -butyl aniline provide anilides that are axially chiral by virtue of restricted rotation about the NAr bond. Rotamer populations about the amide bond (E/Z) were studied by 1 H NMR. Several pairs of enantiomeric o - tert -butyl anilides were separated by chiral chromatography and barriers about the NAr bond were measured by thermal racemization. Related o -(1-(trialkylsilyloxy)-1-methylethyl) anilides were also studied.

Characterization of Chitin and Chitosan Molecular Structure in Aqueous Solution.

Molecular dynamics simulations have been used to characterize the structure of single chitin and chitosan chains in aqueous solutions. Chitin chains, whether isolated or in the form of a β-chitin nanoparticle, adopt the 2-fold helix with ϕ and φ values similar to its crystalline state. In solution, the intramolecular hydrogen bond HO3(n)···O5(n+1) responsible for the 2-fold helical motif in these polysaccharides is stabilized by hydrogen bonds with water molecules in a well-defined orientation. On the other hand, chitosan can adopt five distinct helical motifs, and its conformational equilibrium is highly dependent on pH. The hydrogen bond pattern and solvation around the O3 atom of insoluble chitosan (basic pH) are nearly identical to these quantities in chitin. Our findings suggest that the solubility and conformation of these polysaccharides are related to the stability of the intrachain HO3(n)···O5(n+1) hydrogen bond, which is affected by the water exchange around the O3-HO3 hydroxyl group.

Chitosan molecular structure as a function of N‐acetylation

Molecular dynamics simulations have been carried out to characterize the structure and solubility of chitosan nanoparticle-like structures as a function of the deacetylation level (0, 40, 60, and 100%) and the spatial distribution of the N-acetyl groups in the particles. The polysaccharide chains of highly N-deacetylated particles where the N-acetyl groups are uniformly distributed present a high flexibility and preference for the relaxed two-fold helix and five-fold helix motifs. When these groups are confined to a given region of the particle, the chains adopt preferentially a two-fold helix with ϕ and ψ values close to crystalline chitin. Nanoparticles with up to 40% acetylation are moderately soluble, forming stable aggregates when the N-acetyl groups are unevenly distributed. Systems with 60% or higher N-acetylation levels are insoluble and present similar degrees of swelling regardless the distribution of their N-acetyl groups. Overall particle solvation is highly affected by electrostatic forces resulting from the degree of acetylation. The water mobility and orientation around the polysaccharide chains affects the stability of the intramolecular O3-HO3((n)) ···O5((n +) (1)) hydrogen bond, which in turn controls particle aggregation.

Theoretical studies of liquids by computer simulations: The water-acetone mixture

Abstract Monte Carlo simulation results for pure liquid acetone and water-acetone mixtures calculated in the isothermal and isobaric (NPT) ensemble at T = 298K and p = 1.0atm are presented. The TIP4P model was used for water and optimized potential for liquid simulation (OPLS) force field parameters used for acetone. The results obtained for the average configurational energy as a function of the mole fraction are in good accord with experimental data. Energy partitioning and co-ordination numbers results calculated for equimolar water-acetone solution are compared to similar data obtained for other water-organic liquid mixtures. These results show an increase in water-water interaction energy and co-ordination numbers when the interaction between water and organic liquid molecules decrease. Distribution functions for pure liquid acetone and water-acetone mixtures are presented. Dipole-dipole angular correlation functions obtained for pure liquid acetone show a predominance of dimers with parallel alignment of dipole moments. Radial distribution functions from water-acetone interaction show characteristic features of hydrogen bonded liquids. Radial and angular distribution functions for water-water correlation calculated in pure water and in equimolar water-acetone mixture are compared, showing very similar features in both systems.

Reaction-field–supermolecule approach to calculation of solvent effects

The self-consistent reaction-field formalism has been implemented into the AM1 and MNDO molecular structure codes and has been used to calculate the solvation energies of water and ions in aqueous solution. The interaction of nearby solvent molecules with the solute has been included explicitly by combining the reaction-field formalism with the supermolecule model. The self-consistent reaction-field method was also used to study dielectric effects on tautomeric equilibria. The agreement with the experimental results is good and indicates the usefulness of the combined reaction-field–supermolecule approach for studying solvent effects on chemical processes.

Computer simulation of liquid tetramethylurea and its aqueous solution

Thermodynamic properties and correlation functions for the pure liquid 1,1,3,3-tetramethylurea (TMU) and its aqueous solution were obtained by Monte Carlo simulation in the isothermic and isobaric (NPT) ensemble at 25°C and 1.0 atm. An eight site potential model combining Lennard-Jones plus coulombic functions was developed to calculate intermolecular interaction between TMU molecules. In this model the methyl groups are represented by a united atom approach. The partial charges needed for Coulomb interactions and the geometry of the TMU molecule were calculated at the HF level using a 6-31g* basis set with the CHELPG formalism. The parameters needed for the Lennard-Jones potential functions were optimised to reproduce experimental values for the density and enthalpy of vaporisation of the pure liquid at 298 K and 1.0 atm. The results obtained for density, enthalpy of vaporisation and other thermodynamic properties for the pure liquid TMU are in good agreement with experimental data. Radial distribution functions (rdf) obtained for liquid TMU are broad indicating a low degree of molecular organisation. Dipole–dipole correlation shows a preference for anti-parallel molecular orientation at short distances. Therefore, the present results are consistent with experimental data indicating the formation of dimers due to dipole–dipole interaction. A further test for the potential model was also provided by studying the hydration of TMU on TIP4P water. Potential functions for water–TMU intermolecular interaction were obtained by standard combining rules. The value obtained for the free energy of hydration using statistical perturbation theory was ΔG=-16.82 kJ mol-1, to be compared with the value ΔG=-56.48 kJ mol-1 obtained for urea. Radial distribution functions for water–TMU interaction show features indicating hydrogen bonding between the TMU oxygen site and hydrogen of water. Compared to pure water, our results shows that the water–TMU hydrogen bonding is more stable. The results also show that in dilute TMU–water solution the influence of TMU on the energetics of water–water hydrogen bonding is negligible. Contrasting with gas phase results for the TMU–water dimer the present results do not indicate the formation of hydrogen bonding interaction with the nitrogen site of TMU in aqueous solution. This finding is in agreement with previous hydration studies of dimethylformamide and also with the hydrophobic behaviour of TMU observed in experiments. Dipole–dipole correlation results obtained for TMU and water molecules in the water–TMU solution exhibit significant differences when compared to the ones for the pure liquids.

Interaction between the CBM of Cel9A from Thermobifida fusca and Cellulose Fibers

Molecular docking and molecular dynamics (MD) simulations were used to investigate the binding of a cellodextrin chain in a crystal‐like conformation to the carbohydrate‐binding module (CBM) of Cel9A from Thermobifida fusca. The fiber was found to bind to the CBM in a single and well‐defined configuration in‐line with the catalytic cleft, supporting the hypothesis that this CBM plays a role in the catalysis by feeding the catalytic domain (CD) with a polysaccharide chain. The results also expand the current known list of residues involved in the binding. The polysaccharide‐protein attachment is shown to be mediated by five amine/amide‐containing residues. E478 and E559 were found not to interact directly with the sugar chain; instead they seem to be responsible to stabilize the binding motif via hydrogen bonds. Copyright

Monte Carlo simulation of the binary liquid mixture water—methanol

Abstract Monte Carlo statistical mechanics simulations of water—methanol mixtures were performed in the isothermal—isobaric ensemble (NPT) at T = 298 K and p = 1.0 atm; canonical ensemble (NVT) simulations were performed at this same temperature and experimental densities. Configurational averages were obtained by using Metropolis importance sampling and truncated octahedron box boundary conditions. To calculate the intermolecular energy, the TIP4P and a tree-site model with united atom representation for the methyl group were used for water and methanol molecules respectively. The potential energy surface for water—methanol interaction was calculated using combining rules and the original potential parameters for the pure liquids. Volume contraction and exothermic mixing were obtained in the present calculation, in fair agreement with experimental results. The radial distribution functions obtained show features indicating a large population of hydrogen bonded complexes. The analysis of site—site coordination numbers shows an enhancement of the average number of hydrogen bonded complexes at a methanol composition near 25%. This result agrees with the experimental observation that the water—methanol system has its largest deviation from the ideal mixture behavior at this same composition.

Designing an enzyme-based nanobiosensor using molecular modeling techniques

Nanobiosensors can be built via functionalization of atomic force microscopy (AFM) tips with biomolecules capable of interacting with the analyte on a substrate, and the detection being performed by measuring the force between the immobilized biomolecule and the analyte. The optimization of such sensors may require multiple experiments to determine suitable experimental conditions for the immobilization and detection. In this study we employ molecular modeling techniques to assist in the design of nanobiosensors to detect herbicides. As a proof of principle, the properties of acetyl co-enzyme A carboxylase (ACC) were obtained with molecular dynamics simulations, from which the dimeric form in an aqueous solution was found to be more suitable for immobilization owing to a smaller structural fluctuation than the monomeric form. Upon solving the nonlinear Poisson-Boltzmann equation using a finite-difference procedure, we found that the active sites of ACC exhibited a positive surface potential while the remainder of the ACC surface was negatively charged. Therefore, optimized biosensors should be prepared with electrostatic adsorption of ACC onto an AFM tip functionalized with positively charged groups, leaving the active sites exposed to the analyte. The preferential orientation for the herbicides diclofop and atrazine with the ACC active site was determined by molecular docking calculations which displayed an inhibition coefficient of 0.168 μM for diclofop, and 44.11 μM for atrazine. This binding selectivity for the herbicide family of diclofop was confirmed by semiempirical PM6 quantum chemical calculations which revealed that ACC interacts more strongly with the herbicide diclofop than with atrazine, showing binding energies of -119.04 and +8.40 kcal mol(-1), respectively. The initial measurements of the proposed nanobiosensor validated the theoretical calculations and displayed high selectivity for the family of the diclofop herbicides.