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Jaguar pKa Calculations |
The Jaguar pKa prediction module calculates the pKa (or pKb) of molecules that contain acidic or basic functional groups. The calculations involve geometry optimization of the ionic and neutral species, single-point energy and frequency calculations, and an empirical correction. The accuracy (RMSD) of the prediction is in the range 0.2-0.5 pKa units for bases, and 0.2-1.0 pKa units for acids, depending on the functional group. Empirical corrections have been generated for a wide range of functional groups, including some zwitterions. For groups that are not covered by the specific functional group (specified by SMARTS), more general functional groups are also used, with a larger error in the predicted pKa. The output reports the pKa for all of the functional groups matched, and reports the most accurate value in the Maestro property. The entropic correction for equivalent sites is included in the prediction.
If you want to calculate pKa values without the empirical correction, you can add ipkaraw=1 to the gen section of the input file. The errors in the raw pKa calculations are much higher. You might want to do this, for example, to develop your own empirical correction.
To run a pKa calculation, you can:
The Jaguar panel for pKa prediction has only the Input, SCF, and Solvent tabs, because all other input is predefined.
The structures that you select for the pKa calculation must be the neutral form of the acid or the base. Jaguar does not calculate pKa values for ions, even though one of the calculations must be performed on an ion. These structures must be selected in the Project Table (or Entry List), and are listed in the Input tab.
After selecting structures, you must designate one or more atoms in each molecule as the acidic or basic sites for which the pKa is evaluated. The atom you choose for any site must be the hydrogen atom in an acid, or the basic atom in a base. To designate the sites, click in the pKa Atom cell. You can then either enter the atom names or pick the atoms in the Workspace. If the structure is not already in the Workspace, it is placed in the Workspace (as the only structure).
If you want to perform a conformational search on the protonated and the deprotonated species with MacroModel before the pKa calculation is performed, select Perform conformational searches on input structures. The lowest-energy conformer is used for each species. This option requires a MacroModel license.
If you want to calculate pKa values in DMSO (e.g. for carbon acids), you can choose DMSO from the Solvent option menu in the Solvent tab.
Usually it is not necessary to change any of the SCF convergence settings, but if you want to, you can do so in the SCF tab.
When you have selected the structures and pKa atoms, and made any settings, click Run.
The results of a pKa calculation are returned as a table in
the output text file (.out), and property values are added to the
output structure, which is obtained by optimizing the geometry of the input
structure. The pKa atoms have the pKa value
as an atom property, (pKa water) and the structure has
the pKa value of the first pKa atom as an
entry property.
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