Iván Ortega-Blake

A mobile charge densities in harmonic oscillators (MCDHO) molecular model for numerical simulations: The water–water interaction

In this work we present a new proposal to model intermolecular interactions and use it for water molecules. The parameters of the model were fitted to reproduce the single molecule’s electrostatic properties, a sample of 352 points in a refined ab initio single molecule deformation potential energy surface (PES), and the theoretical limit of the dimerization energy, −20.8 kJ/mol. The model was able to reproduce a sample of 180 additional points in the single molecule deformation PES, and 736 points in a pair-interaction surface computed at the MP2/aug-cc-pVQZ′ level with the counterpoise correction. Though the model reproduced the diagonal of the polarizability tensor, it could account for only 60% of the three-body nonadditive contributions to the interaction energies in 174 trimers computed at the MP2/6-311++(2d,2p) level with full counterpoise correction, but reproduced the four-body nonadditivities in 34 tetramers computed at the same level as the trimers. The model’s predictions of the structures, en...

A comparative study of the hydration of Na+ and K+ with refined polarizable model potentials

The hydrations of Na+ and K+ were investigated by means of Monte Carlo simulations with refined ab initio based potentials. These interaction potentials include intramolecular relaxation, polarizability and many-body nonadditive effects. Care was taken to ensure proper convergence of the MC runs and that the statistical samples were large enough. As a result, agreement was attained with all experimental data available for the hydration of the ions. The water molecules in the first hydration shell were found to have the same intramolecular geometries and dipole moments as those of the bulk. Furthermore, their dipoles were not aligned to the electric field produced by the ion, but quite tilted. The hydration number for the sodium was found to be 5 or 6 water molecules, whereas the potassium’s hydration number had a probability distribution ranging from 5 to 10. From an analysis of the energetic contributions of each hydration shell to the total enthalpy of hydration we propose that the hydrated ions have a ...

On the role of sterol in the formation of the amphotericin B channel

Amphotericin B is an antimycotic agent that has been studied for a long time, both because of its pharmacological action and the interest in understanding how this ionic channel works. It has been proposed that the channel is formed by a barrel of monomers, and that the presence of sterol is needed for the formation of such a barrel. As a matter of fact this need of a sterol has been used as a guiding idea in attempts to design derivatives more efficient in the discrimination of the cholesterol containing membranes, as compared to the ergosterol containing ones, henceforth diminishing the unwanted side effects in its pharmacological use. In this work we show that unitary channels that appear in a cholesterol containing membrane also appear when this membrane is free of cholesterol. We prove this to be the case for two membranes, a biological one, asolectin, and a synthetic one, DMPC. We then advance the idea that the role of sterols in the formation of the amphotericin B channel is related to the effects they have on the structure of the membrane itself, rather than to a direct involvement in the channel formation. We further look into the effect that different cholesterol concentrations in the membrane produce on the single channel properties.

A molecular orbital study of the hydration of ions. The role of nonadditive effects in the hydration shells around Mg2+ and Ca2+

The role of divalent cations in biology, in particular Ca2+ and Mg2+, has led to many studies of the coordination of these ions. The existence of empirical rules serves to characterize these properties, however, a detailed quantum mechanical analysis of the fundamental causes which are responsible for the nature of such properties is lacking. Here, we perform a molecular orbital study of the interactions involved in the hydration scheme of the ions looking particularly into the role of nonadditive effects. Notable differences are found for the cases of Mg2+ and Ca2+.

Nonadditivity in an analytical intermolecular potential: The water–water interaction

We present an analytical potential for intermolecular interactions which includes nonaddivity. We fitted this analytical form to an ab initio energy surface for the water–water interaction and looked into the fidelity of the fitting to two‐body interactions, as well as three‐body and four‐body nonadditives. We tested this potential in a Monte Carlo simulation of liquid water. The results obtained led us to conclude that the model performs very well, giving the best reported fit to the radial distribution functions, the enthalpy per water molecule, and other parameters. The potential appears as an inexpensive, accurate, and flexible potential to be used in numerical simulation studies.

A microscopic electrostatic model for the amphotericin B channel

A microscopic model of an amphotericin B channel is proposed. The structure of the pores is generated using the atomic coordinates of the molecule in the structure determined experimentally by X-ray diffraction. The net charges of the atoms are determined by Mulliken analysis. With these charges the electrostatic energy profiles are calculated for a monovalent ion passing through the channels formed by different number of antibiotic molecules having different radii. The water inside the channel was considered through a continuum medium using the dielectric constant of the bulk, and the membrane contribution was included using the virtual images of the pore in a dielectric slab of epsilon = 3. The model satisfactorily explains the permeability and selectivity characteristics as well as other observations yet unexplained. The electrostatic profiles obtained reinforce the hypothesis of the existence of channels formed by a variable number of units.

Amphotericin B Channels in the Bacterial Membrane: Role of Sterol and Temperature

Amphotericin B is an antibiotic that forms ion channels in the membrane of a host cell. The change in permeability produced by these channels is greatly improved by sterols; nevertheless, the single channel conductivity remains invariant. Hence, it is proposed that sterols do not act directly, but rather through the modulation of the membrane phase. We look at the formation of these channels in the bacterial membrane to determine the mechanism of its known antibiotic resistance. We found that channels can indeed be formed in this membrane, but a substantial amount of amphotericin B is required. We also study the effects of the antibiotic concentration needed for channel expression as well as the dynamics of channels affected by both sterol and temperature in phosphatidylcholine membranes. The results support the idea that membrane structure is a determining factor in the action of the antibiotic.

A refined Monte Carlo study of aqueous urea solutions

In a Monte Carlo study several concentrations of urea in water were studied with a potential that includes polarization and nonadditive effects in the intermolecular interaction. Very long runs, 20×106 steps, were used to assure that equilibrium was attained. The results obtained reproduce experimental data, in particular the nitrogen and hydrogen centered radial distribution functions, validating the model and also allowing for the assignment of the structure of this function. We can also address the phenomena of the dimerization of urea and the urea water correlation. Energetic and structural analysis show that there is a urea network which has a particular effect on water structure.

Development of first-principles interaction model potentials. An application to the study of the bromide hydration

This work presents the development of first-principles bromide ion–water interaction potentials using the mobile charge density in harmonic oscillators-type model. This model allows for a flexible and polarizable character of the interacting molecules and has already been parametrized for water–water interactions. The prospected potential energy surfaces of the bromide ion-water system were computed quantum-mechanically at Hartree–Fock and Moller–Plesset second-order perturbation levels. In addition to the ion–solvent molecule pair, structures formed by the anion and two or three water molecules were considered in order to include many body effects. Minimizations of hydrated bromide clusters in gas phase [Br(H2O)n]− (n=1–6,10,15,20) and Monte Carlo computations of bromide aqueous solutions were performed to test the new potentials. Both structural and thermodynamic properties have been studied in detail and compared to the available experimental and theoretical values. From these comparisons, it was concl...

The role of nonadditive effects in the second hydration shell of Mg2+ and Ca2+. A molecular orbital study of the three‐body potential energy surface

Here we continue [J. Chem. Phys. 76, 5404 (1982)] a quantum mechanical study of the fundamental causes for the different coordination properties of the Mg2+ and Ca2+ ions. We look into the effects of nonadditivity in the second hydration shell, mainly in relation to structure. We also compare our predictions with recent experimental evidence.