Molecular Dynamics Affinity Release Notes

v 6.5.6 March 2025

General Notice

• Structured water analysis in the Short Trajectory MD with Analysis and Analyze Protein-Ligand MD Floes is now turned on by default (Process Water On) in the Trajectory To OEMols Cube. If there is no structured water found near the binding site, it will skip the water analysis.

• A collection handling issue introduced in the Ligand Bound and Unbound Equilibration for NES Floe in the version 6.5.3 has been fixed.

• This version pins orionmdcore==2.5.3, which includes minor bug fixes, including an implementation of a less memory-intense protocol in several cubes, which fixes the risk of out of memory errors witnessed in version 6.5.3 of MD floes. Detailed release notes of version 2.5.3 can be found here: Molecular Dynamics Core Package Release Notes.

• The Compare Experimental Affinity with NES Results Floe was removed because it was redundant with other analysis floes.

v 6.5.3 February 2025

General Notice

• We now support the interactive floe report for the Edge Mapper for RBFE calculations Floe, which allows a user to modify the perturbation map and save the changes as a dataset on Orion.

• A new clustering-based edge map type, a multi-star map, has been added to the Edge Mapper for RBFE calculations Floe, and the star map hub selection scheme has been updated to select the representative parent molecule as a hub.

• This version pins orionmdcore==2.5.1.

• We now print clear error messages in the Floe Failure Report when a rectangular solvation box is chosen without any restraints (along with a Checker Bypass switch of the Bound Protein Ligand MD Health Checker Cube turned OFF). The floe is stopped with a Failed status when that happens. A distance threshold can also be provided to terminate MD runs of ligands if the ligands move beyond that threshold within the binding site after equilibration. This can be done via the shell_cutoff parameter of the Bound Protein Ligand MD Health Checker Cube. The names of those ligands that experience such egress will be noted in the Floe Failure Report. This feature is available in Equilibration and Nonequilibrium Switching, Plain Molecular Dynamics Floe, Ligand Bound and Unbound Equilibration for NES, Bound Protein-Ligand MD, Short Trajectory MD with Analysis, and Solvate and Run MD Floes.

• We allow only one protein molecule as input (not to be confused with multiple chains) to the Short Trajectory MD with Analysis, Ligand Bound and Unbound Equilibration for NES, Equilibration and Nonequilibrium Switching, Solvate and Run MD, Bound Protein-Ligand MD, and Induced-Fit Posing (Confined) Floes. The floes fail quickly when that is found not to be the case.

Floe Updates

• The Short Trajectory MD with Analysis and Analyze Protein-Ligand MD Floes now write the ligand binding interaction occupancy CSV file to the analysis result archive file.

• The Edge Mapper for RBFE calculations Floe by default sets the number of CPUs to run the OEMapper Cube to 48, in order to speed up the perturbation map generation for the large ligand sets.

• The Short Trajectory MD with Analysis Floe carries FreeForm evaluations only when using the FreeForm conformers as unbound sampling starting conformers. By default, the input bioactive conformation is used as a starting conformer for the unbound sampling.

• In the Equilibration and Nonequilibrium Switching Floe, independent choices can be made for the solvation box shapes of the bound and unbound states of ligands. Whereas choosing a rectangular box for the bound state without imposing restraints (unless the Checker Bypass is ON) is still prohibited, box shape choice for the unbound state is not restricted by such restraints. This replicates what has been available in the Short Trajectory MD with Analysis Floe.

• Users can now tune the frequency at which lines reporting the progress of MD production, equilibration, and warm-up stages are printed. They each have a default value (in ns). These defaults are larger than the previously fixed values. The change produces smaller log files that are easier to browse. This affects the Equilibration and Nonequilibrium Switching, Plain Molecular Dynamics Floe, Ligand Bound and Unbound Equilibration for NES, Bound Protein-Ligand MD, Short Trajectory MD with Analysis, and Solvate and Run MD Floes.

• Promoted parameters of the Equilibration and Nonequilibrium Switching, Nonequilibrium Switching Recovery, NES Result Utilities, Nonequilibrium Switching, and Ligand Bound and Unbound Equilibration for NES Floes have been placed in appropriate parameter groups that can be seen in their respective job forms.

• Structured water analysis in the Short Trajectory MD with Analysis and Analyze Protein-Ligand MD Floes is turned off by default (Process Water Off) in the Trajectory To OEMols Cube.

Cube Updates

• The default setting of holonomic constraints in NES has been changed in the NESGMX Cube. This setting now defaults to Bonds2H (default was previously All-Bonds). Along with some other changes to MD settings in NES, this helps to make the MD more numerically stable in NES switches. Although All-Bonds remains a selectable option, it is not recommended because of numerical instabilities in switches involving large mass changes (e.g., hydrogen to bromine).

• A fatal port has been added to the Bound Protein Ligand MD Health Checker Cube for proper exception handling related to box shape choices that are inconsistent with restraints on the solute. Records transmitted through the failure report have also been refined to indicate which ligand moved out of the binding pocket after equilibration.

• A Skip the edge scoring option has been added to the OEMapper Cube to enable the fast star map generation when a user specifies the hub ligand(s) of the star map.