[Jacob Durrant]

Hi Iñigo! I meant to thank you for your very helpful tip. I updated the Gypsum-DL README.md file to mention your suggestion: https://git.durrantlab.pitt.edu/jdurrant/gypsum_dl#getting-started

Take care.

[Jacob Durrant]

Hi William. Much thanks for your interest in AutoGrow4. This error occurs when AutoGrow can’t make enough mutants from the source compounds. I’d recommend using AutoGrow to evolve a larger population of ligands than just two, but you might be able to get it to work by reducing the value of parameters like number_of_mutants, number_of_crossovers, top_mols_to_seed_next_generation, and number_elitism_advance_from_previous_gen. You could also try removing any filters, such as LipinskiLenientFilter.

Hope this helps,

Jacob

[Jacob Durrant]

Hi Taylor. Much thanks for your interest in AutoGrow4. The error might occur when none of the compounds of one generation pass the user-specified filters. You could try increasing the number of crossovers, mutants, etc., to give the program more chances to generate acceptable compounds for advancing to the next generation. Another thing to try is to remove the -LipinskiLenientFilter parameter.

If you’d like to debug whether this error is related to AutoGrow4 installation, you could try using this test file that is included with the AutoGrow4 download: https://git.durrantlab.pitt.edu/jdurrant/autogrow4/-/blob/4.0.3/sample_sub_scripts/sample_submit_autogrow.json

You could also use the docker container if you’re having installation problems: https://git.durrantlab.pitt.edu/jdurrant/autogrow4/-/tree/4.0.3/docker

The error you posted makes me think it’s more a result of the parameters you’re using than an installation error, though.

Hope this helps,

Jacob

[Jacob Durrant]

Thank you for sharing your BASH script with the community, Deepak! It should be helpful for others who run into your same situation. Take care.

[Jacob Durrant]

Hi Taylor. Much thanks for this question, and for your interest in AutoGrow4. I myself had a hard time finding the answer in the documentation. It’s buried in the TUTORIAL.md file: https://git.durrantlab.pitt.edu/jdurrant/autogrow4/-/blob/4.0.3/tutorial/TUTORIAL.md#providing-custom-plugins

...the last column is the diversity fitness and... the second to last column is the metric for "docking/rescored" fitness.

So just to clarify, the penultimate column is the affinity score (e.g., the Vina score), as you guessed. The last column is the diversity score. Here’s an explanation for how the diversity score is calculated, in case it helps: https://jcheminf.biomedcentral.com/articles/10.1186/s13321-020-00429-4#Sec9

Hope this helps. Take care.

~Jacob

[Jacob Durrant]

Hi deepak. Much thanks for your interest in Gypsum-DL. The program automatically adds the __variantX suffix because in some circumstances there are multiple molecular variants for each input molecule. For example, a carboxylate group could be protonated or deprotonated, so there must be some way to distinguish between the two alternately protonated output files.

Since keeping track of these different variants is one of Gypsum-DL’s core functionalities, the renaming is hardcoded and can’t be turned off with a user parameter. You might consider writing a little script (for example in Python or BASH) that renames files if that’s essential for your workflow.

Hope this answer helps. Take care,

Jacob

[Jacob Durrant]

Hi Guillermo,. Much thanks for your interest in BlendMol. To use it, you’ll need to install VMD separately. You can download a copy here: https://www.ks.uiuc.edu/Development/Download/download.cgi?PackageName=VMD

For what it’s worth, on my Mac the path to the executable is /Applications/VMD 1.9.1.app/Contents/vmd/vmd_MACOSXX86

Take care.

[Jacob Durrant]

Hi Alex. Much thanks for pointing out this bug! I just updated the code to fix the issue: https://git.durrantlab.pitt.edu/jdurrant/autogrow4/-/blob/4.0.3/accessory_scripts/fragmenter_of_smi_mol.py#L558

Take care.

[Jacob Durrant]

Hi Nasser. VMD can do the conversion. Just load the trajectory into VMD, click on it’s name in the VMD Main window to select it, right click on the same name to pull up a context menu, click "Save Coordinates…", then put as your "Selected atoms" something like "protein", make sure the File type is set to pdb, and press the "Save…" button.

Here’s a link related to what you want to do, in case it helps: https://www.researchgate.net/post/How_to_write_pdb_file_of_protein_ligand_system_of_a_particular_frame_using_VMD

Take care.

[Jacob Durrant]

Hi Nasser. There are two steps. The first step is to generate a mesh of your protein. BlendMol is the best tool for that. You provide BlendMol with a single-frame PDB file (or a VMD state file), and it imports that file into Blender as a mesh. The PDB file can come from any source (e.g., the Protein Data Bank).

The second step is to animate the mesh by imparting to it the motions present in an MD trajectory file. That MD trajectory file needs to be a multiframe PDB file. (So the trajectory is also a PDB file.) You can convert other trajectory formats to the multiframe PDB format using VMD as well.

Unfortunately, both Blender and VMD are not very user-friendly programs. If you’re not familiar with those programs, you might want to consider other options for visualization, such as PyMol or Chimera.

Best of luck.

[Jacob Durrant]

Happy to hear you got it to work, Rocio! Take care.

[Jacob Durrant]

Hi Nasser. Much thanks for your interest in Pyrite. I’d recommend using BlendMol to generate the mesh to then use in Pyrite, rather than trying to generate the mesh directly in VMD. One of the reasons we created BlendMol is so that users would have to bother with creating the mesh directly. Here’s a video that might help: https://git.durrantlab.pitt.edu/jdurrant/blendmol#video-s3-blendmolpyrite

Take care,

Jacob

[Jacob Durrant]

Hi Nasser. It is possible in Blender to take an existing mesh and to color different parts of it with different materials. This link might help: https://www.youtube.com/watch?v=grwK8QB2DkU

But in my experience, it’s easiest to have one material per mesh. One option would be to set up a VMD state file with just one portion of the protein and to set one material on that imported mesh (e.g., chain A, colored red). Then you could create a second VMD state file with just the other portion of the protein and separately import that with BlendMol (e.g., chain B, colored in green).

Alternatively, you could also just create two separate PDB files, one with each portion of the protein, and then import it directly from within Blender using the BlendMol interface.

Hope this helps! Best of luck with your dissertation.

[Jacob Durrant]

Hi Roco. Much thanks for your interest in AutoGrow4. I believe AutoGrow4 does generate SDF files internally, which it passes to Gypsum-DL for processing. What you’re seeing is more of a warning than an error. AutoGrow4 has created a few ligands that Gypsum-DL apparently can’t handle, so it’s moved on to other compounds.

Can you confirm that it did generate some compounds in the end? As long as it did manage to generate some output ligands, you can safely ignore these warnings.

Take care.

[Jacob Durrant]

Hi Eric. Much thanks for your interest in BlendMol. Unfortunately, .we don’t support PyMol anymore. We found that there are inconsistencies in the way that different versions of PyMol use command-line parameters, and it was difficult to support all possible versions. Currently BlendMol uses VMD as a backend, which provides a consistent command-line interface. More information here: https://git.durrantlab.pitt.edu/jdurrant/blendmol/-/blob/1_3/CHANGES.md#anchor-13

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