Solvation computational modeling

Abstract. Molecular dynamics (MD) simulations of proteins provide descriptions of atomic motions, which allow to relate observable properties of proteins to microscopic processes. Unfortunately, such MD simulations require an enormous amount of computer time and, therefore, are limited to time scales of nanoseconds. We describe first a fast multiple time step structure adapted multipole method (FA-MUSAMM) to speed up the evaluation of the computationally most demanding Coulomb interactions in solvated protein models, secondly an application of this method aiming at a microscopic understanding of single molecule atomic force microscopy experiments, and, thirdly, a new method to predict slow conformational motions at microsecond time scales. 

Floris, F.M. Tomasi, J. Pascal-Ahuir, J.L., Dispersion and repulsion contributions to the solvation energy refinements to a simple computational model in the continuum approximation, J. Comp. Chem. 1991,12, 784-791... 

S. R. Johnson, X. Q. Chen, D. Murphy, O. Gudmundsson, Computational models for the prediction of aqueous solubility that include crystal packing, solvation, and ionization, 232nd ACS National Meeting, San Francisco, CA, United States, Sept. 10-14, 2006, COMP-321. 

Fig. 1. Construction of a computational model for TauD. (A) the solvated TauD enzyme (PDB code 1GY9, solvating water molecules in red) (B) the desolvated enzyme (C) the active site with the substrate and a-ketoglutarate bound to the iron centre, and the most important amino acids in the first and second coordination sphere (D) a minimal model for TauD including only the first coordination sphere and the substrate.

Since binding in solution results from a compromise between interaction with the ligand and solvation, new insights into the origin of the cation recognition process and of the macrocyclic and cryptate effects can be gained from experimental gas phase studies [2.34, 2.35] as well as from computer modelling calculations in vacuo or in a solvent [1.35b, 1.42, 1.43, 1.45, 2.36, 2.37, A.37]. In particular, molecular dynamics calculations indicate that complementarity is reflected in restricted motion of the ion in the cavity [1.45, 2.36]. 

Molecular mechanics is a simple technique for scanning the potential energy surface of a molecule, molecular ion, crystal lattice, or solvate. The model is based on chemical and physical principles. The resulting functions are parameterized on the basis of experimental data. That is, the potential energy surface is computed not by thorough theoretical expressions but by using functions whose parameters are derived empiri-... 

For the first time, solvation continuum models are treated in an up-to-date and coherent way but at the same time using very different points of view coming from experts belonging to very different research fields (mathematicians, theoretical chemists, computational chemists, spectroscopists, etc.). 

Abstract The computational study of excited states of molecular systems in the condensed phase implies additional complications with respect to analogous studies on isolated molecules. Some of them can be faced by a computational modeling based on a continuum (i.e., implicit) description of the solvent. Among this class of methods, the polarizable continuum model (PCM) has widely been used in its basic formulation to study ground state properties of molecular solutes. The consideration of molecular properties of excited states has led to the elaboration of numerous additional features not present in the PCM basic version. Nonequilibrium effects, state-specific versus linear response quantum mechanical description, analytical gradients, and electronic coupling between solvated chromophores are reviewed in the present contribution. The presentation of some selected computational results shows the potentialities of the approach. 

Once the computational model of the molecule is created, it is of most interest to study its properties in the natural environment, in particular, water solvent. Surrounding the molecule with water, allows us to study the solvation process. Like molecules, the solvent may be also described with different levels of accuracy. Beginning with all-atom models of water,48,49 which allow for the studies of solvent structure around solutes but are time consuming and the results are model dependent, to continuous dielectric models,50- 52 which are faster but less accurate and give no knowledge about the solvent itself. Thus, the difference in the level of description for both models is either an advantage or a drawback. These models are commonly known as explicit or implicit solvent models, respectively. 

It can be anticipated that the computation of A//soi and AAsoi is more delicate than the prediction of AGsoi, which benefits from the enthalpy-entropy compensation. Accordingly, the suitability of the QM-SCRF models to predict the enthalpic and entropic components of the free energy of solvation is a challenging issue, which could serve to refine current solvation continuum models. This contribution reports the results obtained in the framework of the MST solvation model [15] to estimate the enthalpy (and entropy) of hydration for a set of neutral compounds. To this end, we will first describe the formalism used to determine the MST solvation free energy and its enthalpic component. Then, solvation free energies and enthalpies for a series of typical neutral solutes will be presented and analyzed in light of the available experimental data. Finally, collected data will be used to discuss the differential trends of the solvation in water. 

Molecular mechanics is a simple technique for scanning the potential energy surface of a molecule, molecular ion, crystal lattice or solvate. The model is based on a set of functions which may or may not be based on chemical and physical principles. These functions are parameterized based on experimental data. That is, the potential energy surface is not computed by fundamental theoretical expressions but by using functions whose parameters are derived empirically by reproducing experimentally observed data. Molecular mechanics then is, similar to a neural network, completely dependent on the facts that it has been taught. The quality of results to be obtained depends on the choice of the experimental data used for the parameterization. Clearly, the choice of potential energy functions is also of some importance. The most common model used is loosely derived from... 

Both AP and Ga have a tightly bound hydrate shell in aqueous solution and both are prone to hydrolysis. In terms of the Hertz electrostatic model for quadrupolar relaxation of ionic nuclei in electrolyte solution (see Section III.C) one therefore expects effective quenching of the electric field gradient caused by the surrounding water dipoles, due to a nearly perfect coordination symmetry. Any contribution to the e.f.g. should therefore arise from outer-sphere solvent dipoles. In terms of the fully orientated solvation (FOS) model this would correspond to a distribution width parameter approaching zero (/. -> 0) with the first term in equation (4) vanishing. This is indeed what Hertz (24) found for both AF" and Ga ", and the experimental infinite dilution relaxation rates ( AP" 7-5 s Ga 350 s ) are remarkably well matched by the computed ones... 

F. Floris and J. Tomasi, /. Comput. Chem., 10, 616 (1989). Evaluation of the Dispersion Contribution to the Solvation Energy. A Simple Computational Model in the Continuum Approximation. 

Realistic three-dimensional computer models for water were proposed already more than 30 years ago (16). However, even relatively simple effective water model potentials based on point charges and Leimard-Jones interactions are still very expensive computationally. Significant progress with respect to the models ability to describe water s thermodynamic, structural, and dynamic features accurately has been achieved recently (101-103). However, early studies have shown that water models essentially capture the effects of hydrophobic hydration and interaction on a near quantitative level (81, 82, 104). Recent simulations suggest that the exact size of the solvation entropy of hydrophobic particles is related to the ability of the water models to account for water s thermodynamic anomalous behavior (105-108). Because the hydrophobic interaction is inherently a multibody interaction (105), it has been suggested to compute pair- and higher-order contributions from realistic computer simulations. However, currently it is inconclusive whether three-body effects are cooperative or anticooperative (109). 

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