Molecular surface area and hydrophobic effect.

Reversibility and Diffusion in Mandelythiamin Decarboxylation. Searching Dynamical Effects in Decarboxylation Reactions

Decarboxylation of mandelylthiamin in aqueous solution is analyzed by means of quantum mechanics/molecular mechanics simulations including solvent effects. The free energy profile for the decarboxylation reaction was traced, assuming equilibrium solvation, while reaction trajectories allowed us to incorporate nonequilibrium effects due to the solvent degrees of freedom as well as to evaluate the rate of the diffusion process in competition with the backward reaction. Our calculations that reproduce the experimental rate constant show that decarboxylation takes place with a non-negligible free energy barrier for the backward reaction and that diffusion of carbon dioxide is very fast compared…

Molecular dynamics simulation in aqueous solution of N -methylazetidinone as a model of β -lactam antibiotics

In this article, we analyze the results of a molecular dynamics simulation in aqueous solution of the N-methylazetidinone molecule, often used to model β-lactam antibiotics. The radial distribution functions (RDFs) corresponding to the most interesting atoms, in terms of reactivity, are presented. We focus our study on the effect of a polar environment on the molecule. The solvent structure around the system is compared to the structure of β-lactam-water complexes, as obtained in a previous study of reaction mechanisms for the neutral and alkaline hydrolyses of N-methylazetidinone. Two types of complexes have been considered which are related to different hydrolysis mechanisms having simila…

Electrostatic interaction of a solute with a continuum. Improved description of the cavity and of the surface cavity bound charge distribution.

Algorithms for a finer description of cavities in continuous media and for a more efficient selection of sampling points on the cavity surface are described. Applications to the evaluation of solute surface and volume and to the calculation of the solute-solvent electrostatic interaction energy, as well as of the cavitation energy are shown as examples.

GEPOL: An improved description of molecular surfaces. III. A new algorithm for the computation of a solvent-excluding surface

To understand and calculate the interactions of a solute with a solvent, a good method of computing the molecular surface is needed. Three kinds of surfaces may be used: the van der Waals Surface, the Accessible Surface, and the Molecular Surface. The latter is redefined in this article as the Solvent-Excluding Surface. The new algorithm for computing the Solvent-Excluding Surface included in the GEPOL93 program is described. GEPOL93 follows the same concept as former versions of GEPOL but with a full new algorithm. Thus, it computes the Solvent-Excluding Surface by filling the spaces not accessible to the solvent with a set of new spheres. The computation is controlled by three parameters:…

A quantum mechanics/molecular mechanics study of the acylation reaction of TEM1 β-lactamase and penicillanate

The acylation step in β-lactamase catalyzed hydrolysis of β-lactams has been explored by means of a quantum mechanics/molecular mechanics approach (AM1/CHARMM). The TEM1 enzyme, a class A β-lactamase, and the penicillanate constitute the system employed in our study. The entire molecular system is divided into a quantum and a classical region: the quantum part is composed by the substrate, the serine Ser70 and the essential moieties of key active site residues, Lys73, Ser130 and Glu166, as well as a water molecule present in the active site region, while the classical part is formed by the remaining residues and structural waters of the enzyme. In particular, the sequence of steps proposed …

Can hydrophobic interactions be correctly reproduced by the continuum models?

The ability of the continuum models to describe hydrophobic interactions is investigated. In this work we have studied the interactions between two methane molecules in aqueous solution by means of a continuum model. The resulting potential of mean force is in good agreement with those obtained using Monte Carlo and molecular dynamics techniques. The three energy contributions appearing in the continuum energy partition (electrostatic, dispersion−repulsion, and cavitation) have been analyzed. The cavitation free energy plays the most important role of the three, determining the existence of an energy barrier between the contact minimum and the separated methane monomers. This barrier, which…

Modeling ?-lactam interactions in aqueous solution through combined quantum mechanics-molecular mechanics methods

A theoretical study of solvent effects on the conformational equilibria of neutral glycine in aqueous solution

Abstract In this work conformational equilibrium of neutral glycine in solution is systematically investigated by using DFT and MP2 methods combined with solvent continuum models. A systematic exploration of the potential energy surface and full geometry optimizations for several conformers have been carried out in the gas phase and aqueous solution at the MP2/6-31+G** and B3LYP/6-31+G** levels. Zero-point and thermal contributions to the free energy have been obtained at the B3LYP level. Both theoretical levels lead to very similar results, in geometrical and energetic terms, both in the gas phase and in solution. Solvent effects play an important role on the conformational equilibria of n…

Continuum-uniform approach calculations of the solubility of hydrocarbons in water

Abstract The ransfer free energies from gas phase to water for some hydrocarbons are calculated by means of a continuum-uniform model of the solvent. For the calculation of the cavitation energy a model based on the surface tension is proposed. The calculated values are compared with the experimental free energies obtained with and without a corrective factor that accounts for the difference in the solute—solvent sizes. Good agreement between the theoretical free energies and the corrected experimental data is obtained. Our calculations seem to show that the hydrophobic effect is directly related to the molecular surface area.

Correlation effects in proton transfer reactions in solution

Abstract The effects of correlation energy on proton transfer reactions in solution for [H 2 OHOH 2 ] + and [NH 3 HH 2 O] + systems have been studied. Solvent effects have been represented by means of a continuum model. The proton transfer energy profiles for fixed proton donor-proton acceptor distances have been obtained in the gas phase and in solution, both at the HF/6-311G ∗∗ and MP2/6-311G ∗∗ //HF levels of theory. Differences between the correlation energies calculated in the gas phase and in solution are negligible, showing that solvent effects can be correctly described for these proton transfer processes at the HF level.

Aminoacid zwitterions in solution : Geometric, energetic, and vibrational analysis using density functional theory-continuum model calculations

Glycine and alanine aminoacids chemistry in solution is explored using a hybrid three parameters density functional (B3PW91) together with a continuum model. Geometries, energies, and vibrational spectra of glycine and alanine zwitterions are studied at the B3PW91/6-31+G∗∗ level and the results compared with those obtained at the HF and MP2/6-31+G∗∗ levels. Solvents effects are incorporated by means of an ellipsoidal cavity model with a multipolar expansion (up to sixth order) of the solute’s electrostatic potential. Our results confirm the validity of the B3PW91 functional for studying aminoacid chemistry in solution. Taking into account the more favorable scaling behavior of density funct…