Introduction

MD Affinity Floes

MD Affinity Floes run the molecular dynamics (MD) simulations to predict relative binding affinities.

The FE-NES for Binding Affinity Prediction Floe (see the FE-NES tutorial) is the central floe in this package. Earlier releases split the work of RBFE into two separate MD stages: a light, fast MD screening stage followed by a computationally more intensive free energy calculation stage. That architecture has been simplified: both stages, along with ligand/edge mapping, equilibrium MD, the nonequilibrium switching (NES) calculations, and the affinity analysis and reporting, are now implemented in the single FE-NES for Binding Affinity Prediction Floe. A prepared protein and a set of ligands are sufficient to obtain predicted relative binding free energies.

Running the steps separately is still supported for staged triage. In that workflow, the MD portion is run first, and its output dataset is then provided as input to the FE-NES for Binding Affinity Prediction Floe:

  1. Run MD with Short Trajectory MD with Analysis Floe.

  2. Provide the resulting output dataset to the FE-NES for Binding Affinity Prediction Floe to compute the relative binding free energies.

Several companion floes in this package reference the same FE-NES machinery and are intended to be used alongside the FE-NES for Binding Affinity Prediction Floe. They expose individual stages of the workflow so that a calculation can be resumed, inspected, or extended without rerunning the full pipeline:

  • Result Utilities for FE-NES Floe computes the relative binding free energies and generates the affinity analysis and reports from NES results that have already been produced.

  • Result Recovery for FE-NES Floe recovers and reassembles results from an interrupted or partially completed FE-NES run, avoiding the cost of repeating the completed edges.

The MD floes used for the staged workflow described above – Short Trajectory MD with Analysis and Extend MD Simulations – also belong to this group, since their output datasets are accepted directly by the FE-NES for Binding Affinity Prediction Floe. Because all of these floes consume and emit the same dataset formats, their outputs can be fed back into the FE-NES for Binding Affinity Prediction Floe to recover results from an interrupted run, add new edges to an existing map, or regenerate the analysis and reports from previously computed trajectories.

A complete list of floes in this package can be found in the MD Affinity Floes Documentation.

Important note about floe editing in this package

Editing these floes in the Orion UI may not work due to the complex data structure used in the data stream between cubes.