Changes PLB from openfe

[hannahbaumann]

As discussed with @ijpulidos and @jchodera , here the PR from the changes that we made to the PLB.

See below for a list of things that have been changed in this PR.

Benchmarking results obtained using this PR:

• https://docs.google.com/document/d/1Gk1LCH8OyPrJnel8dPfmcRw0IVTF1y1Pizo4inO_1jQ/edit?usp=sharing
• cdk2, hif2a, mcl1, p38, pde2, pfkfb3, ptp1b, shp2, tyk2
• Some calculations are still running, this document will be updated as more calculations finish
• We will move to a better way of storing our benchmarking data in the future

Systems that have not been benchmarked yet as they involve net charge changes:

• cdk8, cmet, eg5, syk, thrombin, tnks2

We added tags to the systems in a separate PR, highlighting some challenges of the specific systems

• Add comments to the target.yaml files OpenFreeEnergy/protein-ligand-benchmark#14

Some additional notes on potential problems that could be fixed in future releases of the PLB:

• Notes on things that could be changed in the future OpenFreeEnergy/protein-ligand-benchmark#15

[ijpulidos]

@hannahbaumann , this is amazing work! Thanks for this contribution. I checked the connectivity of the networks and I found out that some of them are disconnected (maybe that's expected?). Specifically:

TARGET: cdk8
NETWORK: 03_edges/lomap_mapper_lomap_network.yml, is connected: False
NETWORK: 03_edges/lomap_mapper_lomap_network_no_element_changes.yml, is connected: False

TARGET: eg5
NETWORK: 03_edges/lomap_mapper_lomap_network.yml, is connected: False
NETWORK: 03_edges/lomap_mapper_lomap_network_no_element_changes.yml, is connected: False

TARGET: syk
NETWORK: 03_edges/lomap_mapper_lomap_network.yml, is connected: False
NETWORK: 03_edges/lomap_mapper_lomap_network_no_element_changes.yml, is connected: False

TARGET: thrombin
NETWORK: 03_edges/lomap_mapper_lomap_network.yml, is connected: False
NETWORK: 03_edges/lomap_mapper_lomap_network_no_element_changes.yml, is connected: False

TARGET: tnks2
NETWORK: 03_edges/lomap_mapper_lomap_network.yml, is connected: False
NETWORK: 03_edges/lomap_mapper_lomap_network_no_element_changes.yml, is connected: False

I took the liberty to do a basic inspection/visualization of the networks and print the "disconnected components" (at least the smallest ones). You can check that at the bottom of this notebook, just in case it helps to know which are the ligands that are disconnected.

[hannahbaumann]

Thank you so much @ijpulidos , this is super helpful! It looks like it's the 5 systems that involve net charge changes. I'll be looking into this!

[IAlibay]

Not had time to look at this sorry - Just a quick 2 mins input, I think some of the ligands.yaml entries for the formal charges need changing.

[hannahbaumann]

@ijpulidos : Here are the input .graphml files for systems MCL1, TYK2, p38, cdk2, hif2a:
ligand_network_mcl1.graphml.zip
ligand_network_tyk2.graphml.zip
ligand_network_p38.graphml.zip
ligand_network_cdk2.graphml.zip
ligand_network_hif2a.graphml.zip

[ijpulidos]

I think Lomap has been modified to be able to generate connected networks when net charge transformations are present. We should probable regenerate these networks here with the latest version of lomap.

[ijpulidos]

Not had time to look at this sorry - Just a quick 2 mins input, I think some of the ligands.yaml entries for the formal charges need changing.

@IAlibay Can you specify which ones? And should we capture this in this PR or make the issue and handle it in another one?

[ijpulidos]

I checked the connectivity again and it seems fine. Looks good for me, thanks!