Result Utilities for FE-NES

Category Paths

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

  • Product-based/Molecular Dynamics

  • Role-based/Computational Chemist

  • Role-based/Medicinal Chemist

  • Task-based/Affinity Prediction

  • Solution-based/Hit to Lead/Affinity Prediction/Free-Energy Calculations

  • Solution-based/Small Molecule Lead-opt/Affinity

Description

  • Purpose:

    • This floe postprocesses a dataset resulting from a free-energy nonequilibrium switching (FE-NES) Floe to perform a comparison with a set of experimental ligand binding free energies (affinities) if the experimental data is provided/present. It can also be used to merge results from FE-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 FE-NES run(s).

      • Orion dataset(s) containing equilibrium run data (in the bound state) for every single ligand of an edge on which FE-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:

    • FE-NES for Binding Affinity Prediction

    • Result Recovery for FE-NES

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 FE-NES Floe, this floe also requires as input the dataset for the bound ligands that was used as input in the FE-NES Floe; this enables an output dataset to be written from this floe that contains the realigned calculated affinities. This floe also produces two Floe Reports of the same form as those generated by the FE-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 FE-NES datasets coming from different runs; for example, a first set of edges can be merged with a subsequent FE-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): With default naming, this input will be named relative_affinity_predictions (current) or nes_output_dataset (legacy) in an upstream floe.

  • Required

  • Type: data_source

End-State MD Simulations (equilibrium): With default naming, this input will be named md_output/md_output_with_analysis (current) or MD_Bnd_Anlys/MD_Bnd and MD_Unb_Anlys/MD_Unb (legacy bound/unbound MD) in an upstream floe.

  • Required

  • Type: data_source

Experimental Affinities (From Equilibrium Input Dataset)

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

  • Type: field_parameter::any

  • 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 (exp):

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): Select whether the file is delimited by whitespace (including tabs) or commas. 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 (affinity_out): Primary output containing per-molecule affinity predictions computed from the relative affinity predictions.

  • Required

  • Type: dataset_out

  • Default: affinity_predictions

FE-NES Result Archive (nes_results_archive): Tar.gz archive containing FE-NES calculation results.

  • Required

  • Type: dataset_out

  • Default: fe_nes_results_archive

Affinity Predictions Report (affinity_floe_report): Title for the affinity predictions floe report.

  • Type: string

  • Default: Affinity Predictions Report

Edge Map Diagram With Predictions (edge_map_with_pred_floe_report): Title for the edge map diagram with predictions floe report.

  • Type: string

  • Default: Edge Map Diagram with Predictions

Failed Output Dataset (fail_out): Stores information about failed calculations.

  • Required

  • Type: dataset_out

  • Default: Failed Output for Result Utilities for FE-NES