Release Notes

0.1.0 July 2023

General Notice

• This is the first release of OpenEye Cryptic Pocket Detection Floes.

• This package is built using OpenEye-orionplatform==5.1.0, OpenEye-toolkits==2023.1.0, and OpenEye-Snowball==0.26.0.

New Floes

• The package contains the following floes that perform weighted ensemble molecular dynamics (WEMD) simulations and analyze the simulation for cryptic pocket detection.

  • A1. Protein Sampling (for Cryptic Pockets): Solvate and Equilibrate Target Protein: This Floe solvates a target protein in a mixed (water-xenon) solvent or a single solvent (water) and equilibrate it before a WEMD simulation.

  • A2. Protein Sampling (for Cryptic Pockets): Calculate Normal Modes: This Floe computes the normal modes associated with an equilibrated target protein. Selected normal modes are used as progress coordinates for a WEMD simulation.

  • A3a: This Floe launches a WEMD simulation for sampling the conformational dynamics of a target protein along one or two selected normal modes.

  • A3b: This Floe extends a WEMD simulation up to a given number of iterations.

  • A4. Protein Sampling (for Cryptic Pockets): Check for Protein Denaturation: This Floe evaluates the structural integrity of the conformations sampled by a WEMD simulation.

  • B1. Trajectory Analysis (for Cryptic Pockets): Residue-Cosolvent Distances: This Floe computes the per-residue solvent-accessible surface area for conformations sampled by a WEMD simulation performed in a mixed solvent.

  • B1. Trajectory Analysis (for Cryptic Pockets): Per-Residue SASA: This Floe computes residue-cosolvent distances for conformations sampled by a WEMD simulation performed in a mixed solvent or a single solvent.

  • B2. Trajectory Analysis (for Cryptic Pockets): Cluster Conformations: This Floe clusters conformations by similarities in their ‘Residue-Cosolvent Distances’ or ‘Per-Residue SASA’ features.

  • C1. Cryptic Pocket Detection: Cooperative Cosolvent Binding Analysis: This Floe identifies cryptic pockets as groups of residues that exhibit cooperative changes in their cosolvent binding behavior during a WEMD simulation performed in a mixed solvent.

  • C1. Cryptic Pocket Detection: Cosolvent Binding Free Energy Analysis: This Floe identifies cryptic pockets as groups of residues bound to high occupancy cosolvent binding (low binding free energy) sites during a WEMD simulation performed in a mixed solvent.

  • C1. Cryptic Pocket Detection: Exposon Analysis: This Floe identifies cryptic pockets as groups of residues that undergo cooperative changes in their solvent exposure during a WEMD simulation performed in a mixed solvent or a single solvent.

  • C2. Cryptic Pocket Detection: Receptor Creation: This Floe creates design units with receptors constructed from site residues defined for a user specified cryptic pocket.