Edge Mapper for RBFE calculations [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/Data Science/Filtering

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


  • Purpose:

    • This Floe produces ligand pairs or edges to run relative binding free energy (RBFE) calculations.

  • Method Recommendations/Requirements:

    • One inputs is required:

      • A ligand dataset. The provided ligands must have reasonable 3D coordinates, all atoms, and correct chemistry such as bond orders and formal charges should be correctly assigned.

      • Optionally, the user can also import into the mapper Floe a map generated externally, to generate a mapper output dataset of only those edges defined by the external map. The syntax of this external map file is described below.

  • Limitations

    • The provided ligand set should contain similar ligands where a common scaffold is used and functional groups are added to it. Large scaffold mutations should be avoided to improve RBFE and ABFE result errors.

  • Expertise Level:

    • Regular

  • Compute Resource:

    • low

  • Keywords:

    • MD, FECalc

  • Related Floes:

    • Nonequilibrium Switching Recovery [Utility] [FECalc]

Given \(n\) ligands, out of all possible \(n(n-1)/2\) edges, the mapper Floe selects a reasonable subset of the edges with the goal of keeping the computational demand low and providing a high probability of giving accurate RBFE calculations.

The Floe offers three map types: (1) Default map; (2) Star map; and (3) Binary star map.

  1. Default map: Based on the general consensus that the more similar the ligands in the edge are, the more accurate the free energy difference estimation is, edges are selected based on a set of heuristics for chemical similarity measures including the MCS, OpenEye’s proprietary ROCS similarity and the equal charge check.

  2. Star map: star map with a center ligand (hub)

  3. Binary star map: star map with two center ligands and an axle edge

If Star map or Binary star map is selected, a user is expected to provide the name(s) of the hub (reference) ligand(s), or the hub(s) will be automatically selected based on the similarities to other ligands. If the specified hub ligand name(s) does not exist in the provided ligand set, it will also auto-select the hub(s).

The output Floe report shows the similarity scores as numbers in the range [0,1], the higher the score the more similar the more similar the ligands in the edge. The Floe mapper output can be used with the NES Floe to run RBFE calculations.

Additionally, The Mapper Floe can accept a edge text input file as well. In this case the produced map is defined in the provide text file and no attempt to use internal heuristics is done. The text file of edges, describes the map of desired alchemical transformations of one ligand into another; each transformation forms an edges of a connected graph of ligands. The file must have one line per transformation, of format:

ligA_name >> ligB_name

where “ligA_name” and “ligB_name” are the ligand title names for the ligands to be transformed. These ligand names must correspond exactly to those in the provided ligand set.

Promoted Parameters

Title in user interface (promoted name)


Ligand or Bound Equilibrium Dataset (ligands): Ligand or Bound Equilibrium Input Dataset

  • Required

  • Type: data_source

Map type (map_type): ‘Default map’ generates OELOMAP, and if ‘Star map’ or ‘Binary star map’ is selected, a user is expected to provide the name(s) of the hub (reference) ligand(s), or the hub(s) will be automatically selected based on the similarities to other ligands.

  • Type: string

  • Default: Default map

  • Choices: [‘Default map’, ‘Star map’, ‘Binary star map’]

Optional Inputs

Optional Ligand Edge Map file (edges): A User-defined ligand edge map text file

  • Type: file_in

Star Map Parameters

Star map hub ligand names (hub): Names of the center ligands of the star map. For the binary star maps, multiple ligand names separated by commas will be parsed. If none is specified, for the star map, a ligand with the highest similarity to other ligands (the largest sum of edge scores) will be chosen as a hub, and for the binary star map, it will choose the two ligands with the top two highest similarities to other ligands.

  • Type: string