Compare Experimental Affinity with End Point Analysis Results

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/Molecular Dynamics

  • Task-based/Affinity Prediction

  • Solution-based/Hit to Lead/Affinity Prediction/STMD

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

Description

  • Purpose:

    • This floe postprocesses a dataset produced by the Protein-Ligand MD Analysis Floes (e.g., Analyze Protein-Ligand MD, Short Trajectory MD with Analysis) to perform a comparison with a set of experimental ligand binding free energies (affinities).

  • Method Recommendations/Requirements:

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

      • Orion dataset(s) of equilibrium run data of ligands in their bound state.

      • [Optional] Select experimental binding affinities from the Orion dataset containing equilibrium run data, 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

  • Related Floes:

    • Analyze Protein-Ligand MD

    • Short Trajectory MD with Analysis

Promoted Parameters

Title in user interface (promoted name)

Inputs

End-State MD Simulations (equilibrium): With default naming, this input will be named md_output_with_analysis (current) or MD_Bnd_Anlys and MD_Unb_Anlys (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

Show comparison in units of (units_out): Units in which affinity comparison is to be displayed

  • Type: string

  • Default: kcal/mol

  • Choices: [‘kcal/mol’, ‘kJ/mol’]

Comparison Output Dataset (comparison_out): Comparison output dataset.

  • Required

  • Type: dataset_out

  • Default: comparison_output

Failed Output Dataset (fail_out): Output dataset of failed calculations.

  • Required

  • Type: dataset_out

  • Default: Failed Output for Compare Experimental Affinity with End Point Analysis Results