MultistatePKaModel Based Ionization States Enumeration Floe

Category Paths

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

  • Role-based/Medicinal Chemist

  • Product-based/QUACPAC

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

  • Task-based/Library Prep & Design

Description

This floe enumerates the reasonable ionization state(s) of input molecules at a neutral/physiological pH (7.4) based on the pKa assessed using a multistate pKa model. The multistate pKa model used in this floe assesses the pKa of acidic or basic functional groups of molecules. For all atoms of the input molecule, pKa is assessed as it belongs to one of three classes: Acidic (pKa < 6.4), Basic (pKa > 8.4), and Neutral (6.4 < pKa < 8.4). According to the assessed pKa class for each atom, it is neither ionized or un-ionized at pH 7.4.

Any group with acidic or basic pKa ranges will result in one state, ionized or un-ionized, and a group with a neutral pKa range will result in both states, ionized and un-ionized. Based on how many such functional groups are there in the molecule, and how many states are generated for them, multiple molecules can be generated for all possible combinations of all possible ionization states of acid and base groups.

The generated ionization states replace the input molecule field and can generate multiple rows if more than one ionization state is generated by the multistate pKa model.

The user can switch on the toggle (default is off) to depict the assessed atomic pKa range on generated ionization states. It depicts the ionization state of the molecule with a colored glyph around the atom with Acidic/Basic/Neutral pKa Range. The legend is shown in each image for reference.

Promoted Parameters

Title in user interface (promoted name)

Inputs

Input Dataset (data_in): Dataset to update with title field.

  • Required

  • Type: data_source

Output Dataset

Output Dataset (data_out): Dataset with enumerated ionization states.

  • Required

  • Type: dataset_out

  • Default: data_out

Failed Output Dataset (fail_data_out): Dataset with molecules where pKa calculation was not successful.

  • Required

  • Type: dataset_out

  • Default: fail_data_out

pKa Enumeration Parameters

Depict Atomic pKaRange (Depict Atomic pKaRange): Switch on/off whether to depict atomic pKaRange or not.

  • Required

  • Type: boolean

  • Default: False

  • Choices: [True, False]