v 4.0.1 June 2021¶
Non-Equilibrium Switching floes for Relative Binding Free Energy (RBFE) affinity calculations
New knowledge-based ensemble score BintScore for pose stability
Support for taking Posit multi-receptor output as input to protein-ligand MD
OpenFF 1.3.1a1 support
Non-Equilibrium Switching. Relative Binding Free energy calculations and estimate of Binding Affinity, starting from equilibrium MD calculations of the bound and unbound ligands.
Ligand Bound and Unbound Equilibration for NES. Performs the equilibrium MD calculations of the bound and unbound ligands needed for NES, starting from an input protein and a set of posed ligands.
Equilibrium and Non Equilibrium Switching. Equilibrium MD runs followed by Non-Equilibrium Switching, starting from an input protein and a set of posed ligands.
Non-Equilibrium Switching Recovery. This floe attempts to produce results from uncompleted NES runs, starting from the recovery file.
Compare Experimental Affinity with NES Results. Datasets from a completed NES run can be re-analyzed by comparison to a new set of experimental data.
Short Trajectory MD with Analysis. The Bint score analysis has been added and Posit support
Analyze Protein-Ligand MD. The Bint score analysis has been added
Cofactors have been added to the MMPBSA score calculations
BoundUnboundSwitching cube. This cube accept a flask and emit on the bound port the flask containing the a complex while the unbound flask is emitted on the standard output port
RBFECEdgeGathering cube. This cube gathers the MD equilibrium simulation data related to the Bound and Unbound simulations and creates edges used to perform relative binding affinity calculations
NESGMXChimera cube. This cube generates a chimera molecule and injecting it on select frames from the Bound and Unbound simulations for the Gromacs forward and reverse Non-Equilibrium simulations
NESGMX cube.This cubes runs the forward and reverse Bound and Unbound starting equilibrium frames by using Gromacs
NESAnalysis cube. This cube collects the data generated from the Non-Equilibrium runs and calculates the relative binding affinities
PlotNESResults cube. This cube generates plots for the Relative binding affinities and the estimated Absolute Affinities versus the provided experimental data. Relevant statistics are calculated and tabled
PredictDGFromDDG cube. This cube applies the Maximum likelihood Estimator method to predict the absolute binding affinities starting from the relative binding affinities
BintScoreInitialPoseAndTrajectory cube. This cube calculates a trajectory ensemble BintScore relative to an initial pose.
Complex Preparation Cube. This cube has been updated to give better support for clashes detected between the ligands and the other flask components for Posit support
v2.0.0 September 2020¶
Ligand centric cluster Analysis
New Parametrization Engine
OpenFF 1.2.0 (Parsley) support
Solvate and Run Protein-Ligand MD. Runs MD on a Protein-Ligand system
Analyze Protein-Ligand MD. Performs Energetic and Clustering Analysis on the output produced by the
Solvate and Run Protein-Ligand MDfloe
Extract Short Trajectory MD results for Download. Extract the results produced by the
Short Trajectory MD with Analysisfloe as file to download
A new Equilibration IV stage has been added to the Short Trajectory MD floe
MD Componentscube has been added to support the new Parametrization Engine
Support for OpenFF 1.1.0 (Parsley), the March 2020 release from the Open Force Field Initiative
Support for Cuda 10.0
Exposed a new parameter in the
TrajToOEMol Cubeto set the water cutoff distance. This distance is used to select water molecules around the protein-ligand binding site for each trajectory frame and producing a multi conformer water molecule
New default parameters have been set on the STMDA floe
Support for the two force fields from the Open Force Field Initiative: Smirnof99Frosst and OpenFF 1.0.0 (parsley)
A new automatic color style is applied to the clustering in the
Short trajectory MD analysisto match the cluster colors in the Floe Report
Fixed a wrong setting in the
Solvation Cubethat was placing solvent molecules too close to the solute. This could have produced un-realistic results for some systems where water molecules could have been placed inside proteins
Fixed a bug in the GAFF/GAFF2 force field where 1-4 interactions were not correctly scaled
Fixed a bug related to un-wanted ligand atom re-ordering
Fixed a bug in the protein-ligand active site depiction
A new Plain Gromacs floe has been added to perform MD by using Gromacs .tpr files
The Yank solvation free energy floe has been removed
The force field parametrization cube now support open force field 1.0.0 (parsley)
The trajectory to multi conformer cube is now adding to the record protein-ligand binding site close waters. These are used to perform MMPBSA calculations with explicit water
Upgrades to the trajectory analysis in floe
Short Trajectory MD with Analysisexpose key results to the Analyze page and 3D visualization page in Orion.
Fixed bug in setting restraints in GROMACS cubes.
Fixed bug in ordering results in the floe report in floe
Short Trajectory MD with Analysis.
- The MD Spruce Prep Floe has been removed. Proteins must be prepared with the Spruce Prep floes available in the Classic
The calculation of MMPBSA can now be also performed by using explicit waters (still experimental)
The MD Spruce Prep Floe has been removed
The Simple MD Floe has been renamed the Plain MD Floe
- A new cube has been developed to check the record size before writing to the Orion backend
to avoiding floe failures. The new cube has been added to all the floes for sanity check.
- A new cube to estimate the water number around a ligand-protein complex has been developed. The cube is
used in the MMPBSA calculation with the explicit water flag set on
Exposed MMPBSA ensemble average and standard deviation in the Trajectory Poisson-Boltzmann and Surface Area Energies so that it can be displayed in the Analyze page in Orion.
Generate Ligand Floe Report HTML from Protein-Ligand MD Traj Analysis. now generates trajectory average and median molecules for protein and ligand, with one conformer for each major cluster. These are exposed int the 3D visualization page in Orion.
Cluster Ligand Traj OEMol now exposes a link to the per-ligand floe report page so it is available in the Analyze page in Orion.
In Complex Preparation traditional references to the full periodic supermolecular ensemble as a “system” have been replaced with references to a “flask” by analogy with an assay well.
In MDFloeReportCube the floe report now generates tiled links to individual ligands in the same order as the initial list of ligands.
In MDFloeReportCube the floe report tiles now show how many major clusters were found for each ligand.
- Hint interactions and Styles have been removed from receptors and ligands in the Protein, Ligand and FF parametrization
setting cubes that could cause problems along the MD analysis stages (debugging is in progress)
- A bug has been fixed in the ligand Elf10 charging cube that was causing problems when carboxylic acid was present
in a ligand to be charged
- The Trajectory to OEMol, Interaction Energies and PBSA calculation cubes have been updated to account for the explicit
water in the new MMPBSA calculation