To understand and calculate the interactions of a solute with a solvent, a good method of computing the molecular surface is needed.

No abstract

Because of its computational cost, QM/MM simulations are usually carried out using low-quality Hamiltonians, such as semiempirical, which are not always able to provide an accurate potential energy surface. We here propose a simple but efficient way to obtain corrected quantum mechanics/molecular mechanics (QM/MM) potentials of mean force (PMF) for chemical processes in condensed media. By means of dual-level calculations on the QM subsystem, we evaluate a correction energy term by employing either the polarized or the unpolarized wave functions. This energy term is evaluated as a function of the distinguished reaction coordinate biased in the calculation of the PMF. Using a mapping coordinate and splines under tension, its derivatives can be readily included to perform molecular dynamics simulations. The structures selected to evaluate the energy correction are chosen from a reaction path obtained in the condensed media, ensuring then that they are representative of the ensemble of structures sampled during the simulation. We have tested the proposed scheme with two prototypical examples:  the Menshutkin reaction in aqueous solution and the chorismate rearrangement to prephenate catalyzed by Bacillus subtilis chorismate mutase. In both cases the use of interpolated corrections clearly improves the quality of the results.

The algorithm used by the program GEPOL to compute the Molecular Surface (MS), as defined by Richards, is presented in detail. GEPOL starts like other algorithms from a set of spheres with van der Waals radii, centered on the atoms or group of atoms of the molecule. GEPOL computes the MS by first searching the spaces inaccessible to the solvent and consequently filling them with a new set of spheres. Here we study the behavior of the method with its parameters, presenting several examples of application.

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.