pKa Exploration Floe

Category Paths

Follow one of these paths in the Orion user interface, to find the floe.

  • Role-based/Computational Chemist

  • Role-based/Medicinal Chemist

  • Solution-based/Hit to Lead/Properties/pKa

  • Task-based/Library Prep & Design

Description

This floe predicts values of the pKa (the log of the acid dissociation constant, Ka) and generates detailed reports on all micro- and macro-pKas predicted, titration curves, protonation micro-equilibria, and a summary of significant states at each macrostate level. It also includes macro- and microspeciation curves and a LogD plot for pH 0.0 to 14.0. This floe is intended to run on a set of up to a few hundred molecules, since it generates quite large reports, including images and plots.

Promoted Parameters

Title in user interface (promoted name)

Inputs

Small Molecule Dataset to Predict pKa On (new_mols): Small molecule dataset to predict pKa on.

  • Required

  • Type: data_source

Outputs

Macro-pKa Prediction (macro_pka_pred): Dataset with macro-pKa prediction.

  • Required

  • Type: dataset_out

  • Default: Macro-pKa

Significant Microstates (significant_micro_states): Dataset of significant microstates.

  • Required

  • Type: dataset_out

  • Default: Significant micro-states

Significant ionization state molecule field (Ionization_state_field): The field to store the significant ionization state molecule. By default it replaces the PrimaryMolField.

  • Type: field_parameter::mol

Failed Descriptors Calculation (newmols_desc_failed): Dataset of molecules with failed descriptors calculation.

  • Required

  • Type: dataset_out

  • Default: Descriptors failed

Options

Get multiple significant states (get_multiple_states): Choose whether to generate multiple significant states at chosen environment pH and fraction cutoffs

  • Required

  • Type: boolean

  • Default: False

  • Choices: [True, False]

Calculate LogD (calc_logD): Choose whether to calculate LogD value

  • Required

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Environment pH (env_pH): pH of environment in which micro states of the molecule are to be estimated. The value will be rounded to the nearest tenth.

  • Required

  • Type: decimal

  • Default: 7.4

Advanced options

Cutoff for ionizable groups count (ion_groups_count_cutoff): The maximum number of ionizable groups to be processed in detailed micro/macro-pKa prediction and protonation micro-equilibria. These groups are chosen by estimated intrinsic pKa to be around chosen environment pH (default 7.4).

  • Required

  • Type: integer

  • Default: 4

  • Choices: [2, 3, 4, 5]

Percentage cutoff for macro-state (macro_state_fraction_cutoff): Only macro states higher than this percentage cutoff at chosen environment pH will be saved to significant states output dataset.

  • Required

  • Type: integer

  • Default: 20

Percentage cutoff for micro-states within the macro state (tautomer_fraction_cutoff): Only micro states having fraction (tautomer fraction) higher than this percentage cutoff within a selected macro state, will be saved to significant states output dataset.

  • Required

  • Type: integer

  • Default: 35

Supporting experimental pKa data file (supporting_data_filename): Name of the supporting data descriptors file you have already created using the floe ‘Prepare supporting experimental pKa data file’

  • Type: file_in