Solvation Methodology

Prior to solvation, the solute is oriented according to its inertial axes such that the box size needed to accommodate it is minimized (minimizing the number of water molecules). The principal inertial axis is oriented along the viewer s Z axis, for example. Then water molecules are eliminated if any of the three atoms are closer to a solute atom than the contact distance you specify. 

You can add restraints to any molecular mechanics calculation (single point, optimization or dynamics). These might be NMR restraints, for example, or any situation where a length, angle, or torsion is known or pre-defined. Restraints with large force constants result in high frequency components in a molecular dynamics calculation and can result in instability under some circumstances. 

Arestraint (not to be confused with a Model Builder constraint) is a user-specified one-atom tether, two-atom stretch, three-atom bend, or four-atom torsional interaction to add to the list of molecular mechanics interactions computed for a molecule. These added interactions are treated no differently from any other stretch, bend, or torsion, except that they employ a quadratic functional form. They replace no interaction, only add to the computed interactions. 

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Implicit solvation methodology is an actively developing field. Recent reviews of implicit solvent models [2,3,5] include more than 800 references each. Thus it is not possible to examine all the proposed methods here. In the present work we have restricted ourselves to reviewing well-established methods that are actively and... 

Maple, J. R., et al, A polarizable force field and continuum solvation methodology for modeling of protein-ligand interactions. /. Chem. Theor. Comput, 2005.1(4), 694-715. 

Specific Solute-Solute and Solute-Solvent Ejfects A well-known disadvantage of continuum solvation methodologies is their inadequacy to treat strong interachng solute-solvent systems. This does not mean that specihc interactions are totally discarded in such methodologies but that only a portion of them, namely the mean electrostatic contribution, is considered, whereas the other terms, connected to the directionality of the interaction, are missed. 

One of the main drawbacks of continuum solvation methodologies is the lack of the treatment of exphcit solute-solvent interactions such as hydrogen bonding. Therefore, depending on the solute-solvent couple, some spectral features, strictly related to these issues, cannot be correctly reproduced. In order to overtake such hmitations, mixed discrete-continuum approaches have been developed [173-180]. In these approaches, the solute molecule is redefined so as to be composed of the target molecule plus a small number of solvent molecules explicitly interacting with the target. However, the precise definition and number of solvent molecules to be exphcitly included in order to reach physically consistent results is not obvious and depends not only on the system under study but also on... 

The tetraimidosulfate anion [S(NtBu)4] , isoelectronic with 804 , is prepared by a methodology similar to that employed for the synthesis of triimidosulfites. The reaction of the sulfur triimide S(N Bu)3 with two equivalents of LiNH Bu produces the solvated monomeric complex [(thf)4Li2S(N Bu)4] (10.21) (Eq. 10.8). The nucleophilic addition of... 

In a manner similar to that just described for differential thermal analysis, DSC can be used to obtain useful and characteristic thermal and melting point data for crystal polymorphs or solvate species. This information is of great importance to the pharmaceutical industry since many compounds can crystallize in more than one structural modification, and the FDA is vitally concerned with this possibility. Although the primary means of polymorph or solvate characterization s centered around x-ray diffraction methodology, in suitable situations thermal analysis can be used to advantage. 

This chapter summarizes most of the studies reported in the literature to date that use the free energy methodology to calculate relative solvation free energies with explicit solvent. In addition, the results are used to define the current scope and limitations of the methodology. 

The use of electrostatic potentials, defined in the context of DFT, for the calculation of ion solvation energies has been reviewed. It has been shown that physically meaningful ionic radii may be obtained from this methodology. In spite of the fact that the electrostatic potentials for cations and anions display a quite different functional dependence with the radial variable, we have shown that it is still possible in both cases to build up a procedure consistent with the Bom model of ion solvation. 

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