NES Result Utilities [Utility] [FECalc]

Description

  • Purpose:

    • This floe post-processes a dataset resulting from a Nonequilibrium Switching (NES) Floe to perform a comparison with a set of experimental ligand binding free energies (affinities) if the experimental data is provided/present or it can also be used to merge results from NES run datasets.

  • Method Recommendations/Requirements:

    • Two primary inputs are required; one additional primary input is optional. All other fields are supplementary:

      • Orion dataset(s) containing Relative Binding Free Energies of edges from NES run(s).

      • Orion dataset(s) containing equilibrium run data (in the bound state) for every single ligand of an edge on which NES was run.

      • [Optional] Select experimental binding affinities from the Orion dataset containing equilibrium run data (in the bound state), or supply a text file containing ligand names, affinity values, optional uncertainties, and optional units.

  • Limitations

    • Only ligand affinities common to both experimental and calculated datasets can be compared.

  • Expertise Level:

    • Regular

  • Compute Resource:

    • Minimal

  • Keywords:

    • Utility, FECalc

  • Related Floes:

    • Nonequilibrium Switching [MDPrep] [MD] [FECalc]

    • Equilibrium and Nonequilibrium Switching [MDPrep] [MD] [FECalc]

    • Nonequilibrium Switching Recovery [Utility] [FECalc]

Since the calculated affinities are based on RBFE calculations, they need a reference free energy offset: this floe aligns the mean of the calculated affinities with the mean of the experimental data for the ligands in common. In addition to the output dataset from the NES Floe, this floe also requires as input the dataset for the bound ligands used as input in the NES Floe; this enables an output dataset to be written from this floe which contains the realigned calculated affinities. This floe also produces two Floe Reports of the same form as those generated by the NES Floes, one for the calculated RBFE edges (transformations of Ligand A into Ligand B), and one for the realigned calculated affinities. If the optional experimental affinity file is not provided, plots will not be produced and only the DG and DDG tables will be generated. The floe can also be used to merge NES datasets coming from different runs, for example, a first set of edges can be merged with a subsequent NES edge run. If the two sets have common edges, the DDG values of the common edges will be averaged.

Promoted Parameters

Title in user interface (promoted name)

Inputs

NES Input Reader (in): The Dataset produced by the Nonequilibrium Switching

  • Required

  • Type: data_source

Bound Input Dataset (bound): with default naming, this input will be named MD_Bnd_Anlys or MD_Bnd in an upstream Floe

  • Required

  • Type: data_source

Experimental Affinities (From Bound Input Dataset)

Column in the dataset with experimental affinity values (affinity_column): Populated after selecting the dataset.

  • Type: field_parameter::float

  • Default: —

Units for affinity values (units):

Use ‘log’ for pIC50, pKi, etc.

  • Type: string

  • Default: Not selected

  • Choices: [‘Not selected’, ‘kcal/mol’, ‘kJ/mol’, ‘pM’, ‘nM’, ‘uM’, ‘mM’, ‘M’, ‘log’]

Column in the dataset with experimental affinity uncertainties (affinity_error_column): Populated after selecting the dataset.

  • Type: field_parameter::float

  • Default: —

Experimental Affinities (From Text File)

Text file containing experimental affinities (exptl):

Syntax for ASCII file: [Ligand] [Affinity] [Error {optional}] [units {optional}].

Allowed units: kcal/mol, kJ/mol, log, M, mM, uM, nM, pM. Use ‘log’ for pIC50, pKi, etc. Use ‘M’, ‘mM’, ‘uM’, ‘nM’ or ‘pM’ for IC50, Ki, etc.

  • Type: file_in

Delimiter (field_separator): Whitespace (including tabs) or comma. Delimiters cannot be mixed.

  • Type: string

  • Default: whitespace(s)

  • Choices: [‘whitespace(s)’, ‘,’]

Units for affinity values (units_expt_file):

Use ‘log’ for pIC50, pKi, etc. Units present in the experimental file override this selection.

  • Type: string

  • Default: Not selected

  • Choices: [‘Not selected’, ‘kcal/mol’, ‘kJ/mol’, ‘pM’, ‘nM’, ‘uM’, ‘mM’, ‘M’, ‘log’]

Outputs

Affinity Output Dataset (DG): Output dataset of binding affinity calculations.

  • Required

  • Type: dataset_out

  • Default: binding_affinity_output_dataset

NES Failure Dataset (fail): Output dataset of failed calculations.

  • Required

  • Type: dataset_out

  • Default: failed_dataset