Solvation energy models computational studies

The electrostatic solvation energy is only a part of the total solvation energy. Cavitation, dispersion and repulsion terms must be added. We show below that the MPE method leads to similar electrostatic energies than the polarizable continuum model (PCM) of Tomasi and co-workers [10], provided the same cavities are used. Therefore, non-electrostatic terms in these methods may be computed using the same computational strategies [15]. We emphasize the fact that accurate non-electrostatic contributions are often difficult to compute since they are based on parameterized formulae that cannot be directly compared to experiment. The obtained data must therefore be used with prudence, especially if they are expected to play a major role in the process under study. Fortunately, in many circumstances, non-electrostatic terms are small and/or vary little, so that they can be neglected. Tunon et al. [80] developed a parameterized expression for the MPE method using an expression of the type... 

Computational studies investigate reaction mechanisms and pathways by constructing potential energy profiles. This involves exploring reaction thermodynamics and kinetics, by examining reactants and products as well as the transition states geometries and activation energy barriers. Like those seen in structure prediction, most current studies implement effective core potentials and density functional theory to perform calculations.However, ECPs can be paired with MP2 to account for electron correlation thus far, this approach has only been used for smaller chemical systems. " Eurthermore, solvation methods such as the polarizable continuum model can be employed to examine... 

Continuum electrostatic models [72,108-113] are presently most developed and commonly nsed for the evaluation of the solvation energies in proteins however, they carry a nnmber of limitations and uncertainties, which cannot be avoided unless the microscopic interactions of the quantum subsystem and the protein are taken into account [114], For example, it is not clear which dielectric constant of the polarizable water cavities one should use in such calculations even the usually assumed dielectric constant of a dry protein (typically assumed as 4 [99,115,116]) is not that well defined—many studies indicate that the effective dielectric of the protein is much higher [114,117-119]— primarily due to internal water [120], and partially due to protein (nonlinear) charge relaxation. Proteins are also inhomogeneous media. It is understood that only microscopic simulations should eventually provide a correct picture and remove the inherent uncertainty of phenomenological approach [71,114,115,121-132]. Despite the drawbacks, the continuum models provide most computationally efficient approach for the treatment of the protein electrostatics, which make possible large-scale investigation of the enzyme properties, such as CcO. 

The present chapter thus provides an overview of the current status of continuum models of solvation. We review available continuum models and computational techniques implementing such models for both electrostatic and non-electrostatic components of the free energy of solvation. We then consider a number of case studies, with particular focus on the prediction of heterocyclic tautomeric equilibria. In the discussion of the latter we center attention on the subtleties of actual chemical systems and some of the dangers of applying continuum models uncritically. We hope the reader will emerge with a balanced appreciation of the power and limitations of these methods. 

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