The Macro-pKa Input File

The Macro-pKa input file (name.in) contains keyword-value pairs for defining the parameters of the calculation. Keywords whose values are lists (conformer structure files and relative charges) are formatted as comma-separated lists enclosed in square brackets (like a Python list). The keywords are described in Keywords in the Macro-pKa Input File.

The following is an example of the contents of a simple input file:

infile = molecule.mae
relative_charges = [-1, 0, 1]
csrch = 5

Specifying Macro-pKa transitions

There are several ways you can define the macro-pK_a transitions to consider in the calculation. Use the relative_charge keyword to specify transitions from one charge to another by providing a list of relative charges. For example, if a molecule has a total charge of 2, specifying

relative_charges = [3, 2, 1, 0, -1]

corresponds to considering the macro-pK_a transitions of total charges 5 to 4, 4 to 3, 3 to 2, and 2 to 1.

Setting protonate = True is equivalent to setting relative_charges = [0, 1], while setting deprotonate = True is equivalent to setting relative_charges = [0, -1]. While a job will not crash if both relative_charge and protonate/deprotonate keywords are provided, it will give an error if the values of these keywords are in conflict with one another.

You can also set the range of macro-pK_a's to consider using the pka_max and pka_min keywords. See Defining Charge Transitions for more information about how these keywords are used to determine the macro-pK_a transitions to consider.

Conformer generation

Use csrch to specify the maximum number of lowest energy conformers for each tautomer to include in the Macro-pKa calculation. We recommend doing a conformational search with N=2-5 per generated tautomer for larger and more flexible molecules. The conformer search is performed with MacroModel and requires a MacroModel license. By default, a conformation search is not performed (csrch=0).

You can also specify other ways to include conformers in the calculation, for example, by using autoconf_config to include a custom AutoConf config file for generating conformers and tautomers, or conformer_files to include a list of .mae files containing precomputed conformations for each charge.

Please note that you can only use one of these keywords.

Other keywords

Set pH to your preferred pH (for example pH = 8.2) if you want populations of all the species to be computed at this pH (the default is pH = 7.0). The result will be available at the bottom of the *.log file.

If you have a good guess of which protons and heavy atoms will be involved in tautomerization processes for the given molecule, it is possible to specify the “active atoms” that Macro-pKa should consider in its generation of tautomers. This option can significantly reduce the number of tautomers considered. Use the keyword active_atoms followed by a list of atom numbers:

active_atoms = [6, 32, 47, 52]

When tautomers are generated, active hydrogen atoms are distributed among active proton acceptors.

Command syntax

The command syntax for running Macro-pKa from the command line is:

jaguar run macro_pka.py inputfile.in

See macro_pka.py Command Help for command options.