pKa Keywords in the Jaguar Input File

  • Overview
  • Examples

Keywords for controlling aspects of pKa calculations are listed in the table below.

Table 1. Keywords for pKa calculations

Keyword

Value

Description

ipkat

atom

Specify the atom for which the pKa is calculated, using either the atom number or the atom label. The atom should be the acidic hydrogen atom in an acid, or the basic atom in a base.

ipkasites

list

Specify multiple atoms for which to calculate the pKa. The list is a comma-separated list of atom numbers or atom labels (or a mix), with no spaces. The atoms should be the acidic hydrogen atoms in acidic groups, or the basic atoms in basic groups.

ipkasearch

list

Search for pKa atoms in the given list of atoms. The list is a comma-separated list of atom numbers or atom labels (or a mix), with no spaces, or it can be all, meaning the entire molecule. A pKa is calculated for each atom found.

ipka_prot_deprot

both

When searching for sites, look for both protonation and deprotonation sites.

 

protonation

When searching for sites, look for protonation sites only.

 

deprotonation

When searching for sites, look for deprotonation sites only.

ipka_lower_cut

2.0

Specify cutoff for low pKa values. When searching for sites, any atom for which all of the training set pKa values for the functional group are lower than the cutoff is not included in the list.

ipka_upper_cut

12.0

Specify cutoff for high pKa values. When searching for sites, any atom for which all of the training set pKa values for the functional group are higher than the cutoff is not included in the list.

ipka_tier_cutoff

1

Specify the tier in the shell model for which functional groups are excluded the search. All groups in and above this tier are excluded. Tier 0 is the specific groups, tier 1 is the generic groups, tier 2 is everything.

ipkaraw

0

Calculate corrected pKa values.

 

1

Calculate raw pKa values with no empirical correction. These can be used for fitting to obtain new corrections.

ipka_max_conf

5

Specify the maximum number of conformers to use in the pKa calculations. When multiple conformers are specified, a macroscopic pKa is calculated. The conformers are generated by MacroModel and then optimized by Jaguar.

ipka_erg_window

12.0

Discard conformers if their energy relative to the lowest energy conformer is higher than the specified value, in kcal/mol.

ipkaverbose

0

Do not print more output for macroscopic pKa calculations.

 

1

Print more output for macroscopic pKa calculations, including intermediate pKa(i,j) values.

ipka_csrch_acc

0

Use the standard accuracy parameters for MacroModel conformational searches (100 steps, 500 minimization iterations).

 

1

Use higher accuracy parameters for MacroModel conformational searches (3000 steps, 2500 minimization iterations). This is useful for reducing or eliminating dependence on input structures and providing better coverage of conformational space.

ipka_solv_opt

0

Run Jaguar optimizations in the gas phase.

 

1

Run Jaguar optimizations in solution.

ipka_frac_gconf

0.0

Specify the fraction of conformers out of the total number (ipka_max_conf) to be optimized in the gas phase. The fraction of conformers to be optimized in solution is one minus this number. Both sets of conformers, gas phase and solution phase, are taken from the pool produced by MacroModel, starting with the lowest in energy. Both sets are used to calculate the macroscopic pKa. The use of both gas-phase and solution-phase optimized conformers helps to ensure good coverage of the low-energy conformational space.

ipkasymm

0

Turn off the entropic correction for equivalent sites.

 

1

Calculate the entropic correction for equivalent sites.

Workflow Examples

Note: Sites to remove H+ or add H+ are specified by ipkasites keyword. Comma delimited lists denote each atom to assess. Can also perform an automated search of potential basic atoms or acidic hydrogens by setting ipkasites=all. To model a sequential dissociation (pKa2) you would have to start with a singly dissociated molecule in the workspace.

Example input file (wflow-pka_jaguar-0001.in):

&gen
ipka_prot_deprot=both
ipkasites=H5
ipka_lower_cut=2.0
ipka_upper_cut=6.0
ipka_solv_opt=1
ipka_max_conf=3
ipka_csrch_acc=0
&
&zmat
C1     -0.4163000000000   0.5181000000000   2.4848000000000
O2      0.5557000000000   1.2181000000000   2.6175000000000
H3     -1.2388000000000   0.4240000000000   3.2102000000000
O4     -0.6643000000000  -0.2721000000000   1.4224000000000
H5      0.0829000000000  -0.1601000000000   0.8080000000000
&

To submit the job from the command line, download the input file (below) and enter the following command:

$SCHRODINGER/jaguar run pka.py -n -csrch -jobname=wflow-pka_jaguar-0001 wflow-pka_jaguar-0001.in

Click a button to download the file. The Output files are those produced when the job is run.

Files generated with release version: 2024-4

Input file: wflow-pka_jaguar-0001.in
Output files

Note: The pKa predictions were assessed in the range of 2-12, according to defaults.

Example input file (wflow-pka_macro-0001.in):

csrch = 2
infile = wflow-pka_macro-0001.mae

Example input structure file (wflow-pka_macro-0001.mae):

{ 
 s_m_m2io_version
 :::
 2.0.0 
} 

f_m_ct { 
 s_m_title
 i_m_ct_enhanced_stereo_status
 s_m_entry_id
 s_m_entry_name
 b_sd_chiral_flag
 i_sd_version
 s_m_Source_Path
 s_m_Source_File
 i_m_Source_File_Index
 i_m_ct_format
 :::
 Structure1 
  0
  1 
  pyr.1 
  0
  0
  /Users/moore1 
  pyr.xyz 
  1
  2
 m_atom[10] { 
  # First column is atom index #
  i_m_mmod_type
  r_m_x_coord
  r_m_y_coord
  r_m_z_coord
  i_m_residue_number
  i_m_color
  i_m_atomic_number
  s_m_color_rgb
  :::
  1 25 -1.197600 1.984000 -0.094600 900 43 7 5757FF 
  2 2 -0.019800 1.395800 -0.069000 900 2 6 A0A0A0 
  3 2 1.196700 2.074200 -0.035000 900 2 6 A0A0A0 
  4 2 1.093800 3.460700 -0.029300 900 2 6 A0A0A0 
  5 25 -0.083900 4.104900 -0.054600 900 43 7 5757FF 
  6 2 -1.165400 3.324700 -0.086000 900 2 6 A0A0A0 
  7 56 -0.016400 0.060300 -0.076800 900 8 9 00FF7F 
  8 41 2.143300 1.549000 -0.014700 900 21 1 FFFFFF 
  9 41 1.987200 4.080800 -0.003600 900 21 1 FFFFFF 
  10 41 -2.129800 3.826200 -0.106900 900 21 1 FFFFFF 
  :::
 } 
 m_bond[10] { 
  # First column is bond index #
  i_m_from
  i_m_to
  i_m_order
  :::
  1 1 6 2
  2 1 2 1
  3 2 3 2
  4 2 7 1
  5 3 4 1
  6 3 8 1
  7 4 9 1
  8 4 5 2
  9 5 6 1
  10 6 10 1
  :::
 } 
}

To submit the job from the command line, download the input files (below) and enter the following command:

$SCHRODINGER/jaguar run macro_pka.py -jobname=wflow_pka_macro_0001 wflow-pka_macro-0001.in

Click a button to download the file. The Output files are those produced when the job is run.

Files generated with release version: 2026-1

Input file: wflow-pka_macro-0001.in
Input structure: wflow-pka_macro-0001.mae
Output files