NES Result Utilities [Utility] [FECalc]

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 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 file is provided or it can also be use to merge results from NES run datasets.

  • Method Recommendations/Requirements:

    • Two inputs are needed:

      • A required output dataset of edges (DeltaDeltaGs) from an NES Floe.

      • An optional text file containing experimental binding free energies for at least one ligand, one experimental datapoint per line, of form ligA_name DeltaG(exptl) error_DeltaG(exptl) units for example: gn1c -8.56 0.17 kcal/mol

  • 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: the 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 just 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 a first set of edges can be merge with a subsequent nes edge run. If the two sets have common edges, the DDGs values of the common edges wil be averaged.

Promoted Parameters

Title in user interface (promoted name)

  • Affinity Out (DG) type: dataset_out: Affinity Out
  • Bound Equilibrium Reader (bound) type: data_source: The Equilibrium Bound Dataset
  • Ligand Experimental Results (exptl) type: file_in: Ligand Experimental Results
  • Failures (fail) type: dataset_out: Fail Data Set
  • NES Input Reader (in) type: data_source: The Dataset produced by the Nonequilibrium Switching

Optional parameters (promoted names)

  • NES Input Reader (data_in) type: data_source: The Dataset produced by the Nonequilibrium Switching
  • Output Dataset (nes_data_out) type: dataset_out: Output dataset to write to
  • Affinity Out (data_out) type: dataset_out: Affinity Out
  • Failures (data_out) type: dataset_out: Fail Data Set
  • Bound Equilibrium Reader (data_in) type: data_source: The Equilibrium Bound Dataset
  • Ligand Experimental Results (lig_exp_file) type: file_in: Ligand Experimental Results