Compare Experimental Affinity with NES Results [Utility] [FECalc]

Category Paths

  • 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 nonequilibrium switching (NES) Floe to perform a comparison with a set of experimental ligand binding free energies (affinities).

  • Method Recommendations/Requirements:

    • Two inputs are required:

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

      • A 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:

    • Non Equilibrium Switching [MDPrep] [MD] [FECalc]

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

    • Non-Equilibrium 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 additon 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.

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 Non-Equilibrium Switching