Lightdock in google colab

[lightdock]

Lightdock in google colab

[andresilvapimentel]

Yes, it is. Em qui, 25 de fev de 2021 13:35, Brian Jimenez <[email protected]> escreveu:

…

This is the correct pipeline according to your input: !lightdock3_setup.py rec.pdb lig.pdb -s 100 -g 80 !lightdock3.py -s mj3h setup.json 10 -l 0 !lgd_generate_conformations.py --setup setup.json rec.pdb lig.pdb swarm_0/gso_10.out 80 !lgd_cluster_bsas.py swarm_0/gso_10.out Please make sure rec.pdb and lig.pdb files are available in your Colab env. — You are receiving this because you authored the thread. Reply to this email directly, view it on GitHub <#11 (comment)>, or unsubscribe <https://github.com/notifications/unsubscribe-auth/AS3PBBK6R7DTBQA52YSQP23TAZ34ZANCNFSM4X5JHYNA> .

[andresilvapimentel]

It works fine now!!! Thanks.

[brianjimenez]

A couple of comments on lgd_cluster_bsas.py:

1. Script is expecting to be executed from inside the swarm_M directory where the gso_N.out file is located.
2. All structures from gso_N.out are expected to have been generated with lgd_generate_conformations.py.

So instead of only generating 10 conformations on that folder, please try again generating all of them and then running lgd_cluster_bsas.py inside the swarm_M directory.

[andresilvapimentel]

Dear Brian,
Thank you for your comments. Yes, I did exactly what your commented. I double checked it now to make sure I was doing exactly what you suggested.
I am not sure why It is looking for the lightdock_17.pdb file because I only generate 10 conformations.
Do you know why?

[andresilvapimentel]

Another issue...
I was trying to perform a flexible docking running the following command for setting up the system:

!lightdock3_setup.py -anm -anm_lig 10 -anm_rec 10 receptor.pdb ligand.pdb 100 80

Then, running the docking simulation with:
!lightdock3.py -s mj3h setup.json 10

The error message is:
[0] step 1
Process Tentacle-1:
Traceback (most recent call last):
File "/usr/lib/python3.6/multiprocessing/process.py", line 258, in _bootstrap
self.run()
File "/usr/local/lib/python3.6/dist-packages/lightdock/parallel/kraken.py", line 20, in run
task.run()
File "/usr/local/lib/python3.6/dist-packages/lightdock/parallel/util.py", line 12, in run
saving_path=self.saving_path, save_intermediary=True)
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/algorithm.py", line 38, in run
self.swarm.update_luciferin()
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/swarm.py", line 21, in update_luciferin
glowworm.compute_luciferin()
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/glowworm.py", line 49, in compute_luciferin
self.scoring = sum([landscape_position.evaluate_objective_function() for landscape_position in self.landscape_positions])
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/glowworm.py", line 49, in
self.scoring = sum([landscape_position.evaluate_objective_function() for landscape_position in self.landscape_positions])
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/searchspace/landscape.py", line 151, in evaluate_objective_function
self.receptor_pose.coordinates += self.receptor.n_modes[i] * self.rec_extent[i]
TypeError: 'NoneType' object is not subscriptable
[1] step 1
Process Tentacle-2:
Traceback (most recent call last):
File "/usr/lib/python3.6/multiprocessing/process.py", line 258, in _bootstrap
self.run()
File "/usr/local/lib/python3.6/dist-packages/lightdock/parallel/kraken.py", line 20, in run
task.run()
File "/usr/local/lib/python3.6/dist-packages/lightdock/parallel/util.py", line 12, in run
saving_path=self.saving_path, save_intermediary=True)
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/algorithm.py", line 38, in run
self.swarm.update_luciferin()
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/swarm.py", line 21, in update_luciferin
glowworm.compute_luciferin()
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/glowworm.py", line 49, in compute_luciferin
self.scoring = sum([landscape_position.evaluate_objective_function() for landscape_position in self.landscape_positions])
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/glowworm.py", line 49, in
self.scoring = sum([landscape_position.evaluate_objective_function() for landscape_position in self.landscape_positions])
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/searchspace/landscape.py", line 151, in evaluate_objective_function
self.receptor_pose.coordinates += self.receptor.n_modes[i] * self.rec_extent[i]
TypeError: 'NoneType' object is not subscriptable
[kraken] INFO: 100 ships destroyed
[lightdock] INFO: Finished.

Do you know what I am doing wrong?

[brianjimenez]

Sorry, Mj3h scoring function does not support ANM as it's not a full-atom scoring function.

Another issue...
I was trying to perform a flexible docking running the following command for setting up the system:

!lightdock3_setup.py -anm -anm_lig 10 -anm_rec 10 receptor.pdb ligand.pdb 100 80

Then, running the docking simulation with:
!lightdock3.py -s mj3h setup.json 10

The error message is:
[0] step 1
Process Tentacle-1:
Traceback (most recent call last):
File "/usr/lib/python3.6/multiprocessing/process.py", line 258, in _bootstrap
self.run()
File "/usr/local/lib/python3.6/dist-packages/lightdock/parallel/kraken.py", line 20, in run
task.run()
File "/usr/local/lib/python3.6/dist-packages/lightdock/parallel/util.py", line 12, in run
saving_path=self.saving_path, save_intermediary=True)
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/algorithm.py", line 38, in run
self.swarm.update_luciferin()
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/swarm.py", line 21, in update_luciferin
glowworm.compute_luciferin()
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/glowworm.py", line 49, in compute_luciferin
self.scoring = sum([landscape_position.evaluate_objective_function() for landscape_position in self.landscape_positions])
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/glowworm.py", line 49, in
self.scoring = sum([landscape_position.evaluate_objective_function() for landscape_position in self.landscape_positions])
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/searchspace/landscape.py", line 151, in evaluate_objective_function
self.receptor_pose.coordinates += self.receptor.n_modes[i] * self.rec_extent[i]
TypeError: 'NoneType' object is not subscriptable
[1] step 1
Process Tentacle-2:
Traceback (most recent call last):
File "/usr/lib/python3.6/multiprocessing/process.py", line 258, in _bootstrap
self.run()
File "/usr/local/lib/python3.6/dist-packages/lightdock/parallel/kraken.py", line 20, in run
task.run()
File "/usr/local/lib/python3.6/dist-packages/lightdock/parallel/util.py", line 12, in run
saving_path=self.saving_path, save_intermediary=True)
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/algorithm.py", line 38, in run
self.swarm.update_luciferin()
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/swarm.py", line 21, in update_luciferin
glowworm.compute_luciferin()
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/glowworm.py", line 49, in compute_luciferin
self.scoring = sum([landscape_position.evaluate_objective_function() for landscape_position in self.landscape_positions])
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/glowworm.py", line 49, in
self.scoring = sum([landscape_position.evaluate_objective_function() for landscape_position in self.landscape_positions])
File "/usr/local/lib/python3.6/dist-packages/lightdock/gso/searchspace/landscape.py", line 151, in evaluate_objective_function
self.receptor_pose.coordinates += self.receptor.n_modes[i] * self.rec_extent[i]
TypeError: 'NoneType' object is not subscriptable
[kraken] INFO: 100 ships destroyed
[lightdock] INFO: Finished.

Do you know what I am doing wrong?

[brianjimenez]

I've never tested LightDock from a notebook, I guess some path assumption might be wrong. Would you mind sharing this notebook together with the input PDB files? Then I would try to test it on Jupyter Notebook and Colab.

Dear Brian,
Thank you for your comments. Yes, I did exactly what your commented. I double checked it now to make sure I was doing exactly what you suggested.
I am not sure why It is looking for the lightdock_17.pdb file because I only generate 10 conformations.
Do you know why?

[brianjimenez]

Error message will be improved in #12

[andresilvapimentel]

I can share it, sure. I am using the test example in the tutorial. It is pretty straightforward. I just turned my computer off and closed for the weekend.
If you want, you can just install lightdock using pip, and use the basic commands, very easy. It works fine, except the cluster analysis

[brianjimenez]

Implemented in version 0.9.0a2, tested on Google Colab: !pip install lightdock==0.9.0a2

https://colab.research.google.com/gist/brianjimenez/927f0749fbabf943e472f95d87bd425b/lightdock_101.ipynb

Please reopen issue if you experience any issue concerning lgd_cluster_bsas.py.

[andresilvapimentel]

Dear Brian,
I opened your colab notebook above and worked fine with the commands:
!lightdock3_setup.py 2UUY_rec.pdb 2UUY_lig.pdb -s 100 -g 80
!lightdock3.py setup.json 20 -s fastdfire -l 0
!lgd_generate_conformations.py 2UUY_rec.pdb 2UUY_lig.pdb swarm_0/gso_20.out 80
!lgd_cluster_bsas.py swarm_0/gso_20.out

Then, I tried to perform the same with my receptor and ligand using the following commands:
!lightdock3_setup.py rec.pdb lig.pdb -s 100 -g 80
!lightdock3.py -s mj3h setup.json 10 -l 0
!lgd_generate_conformations.py --setup setup.json rec.pdb lig.pdb swarm_38/gso_10.out 10
!lgd_cluster_bsas.py swarm_38/gso_10.out

The error message was:
[lgd_cluster_bsas] INFO: Reading CA from /content/swarm_11/lightdock_68.pdb
[lgd_cluster_bsas] ERROR: Clustering has failed. Please see error:
[lgd_cluster_bsas] ERROR: object of type 'PosixPath' has no len()

I repeated this for a couple systems to check if anything was wrong with files, but none worked for me showing up the same message.
I am not sure if the mj3h score function works with clustering. I used the mj3h score function with your notebook and worked fine.

Another comment... When I run !lightdock3_setup.py rec.pdb lig.pdb -s 100 -g 80

[pdb] WARNING: Possible problem: [SideChainError] Incomplete sidechain for residue ILE.5
[pdb] WARNING: Possible problem: [SideChainError] Incomplete sidechain for residue ILE.9

I am not sure if this can cause any issue. I hope you know what is going on.

[brianjimenez]

!lightdock3_setup.py rec.pdb lig.pdb -s 100 -g 80
!lightdock3.py -s mj3h setup.json 10 -l 0
!lgd_generate_conformations.py --setup setup.json rec.pdb lig.pdb swarm_38/gso_10.out 10
!lgd_cluster_bsas.py swarm_38/gso_10.out

Problem here is that you are only simulating swarm 0 (please note the -l 0 flag which means only run for swarm 0).
Then, lgd_generate_conformations.py --setup setup.json rec.pdb lig.pdb swarm_38/gso_10.out 10 is failing to generate the predicted structures since the swarm 38 is not the one simulated on previous step.
Final clustering fails because of the same reason.

About the warning, is just a way of flagging incomplete side chains, which might affect the quality of predictions if that residue is for example part of the interface.

[andresilvapimentel]

My first try was without -l 0 which It did not work it. Then, I tried with -l 0 and it did not work it as well.

[brianjimenez]

This is the correct pipeline according to your input:

!lightdock3_setup.py rec.pdb lig.pdb -s 100 -g 80
!lightdock3.py -s mj3h setup.json 10 -l 0
!lgd_generate_conformations.py --setup setup.json rec.pdb lig.pdb swarm_0/gso_10.out 80
!lgd_cluster_bsas.py swarm_0/gso_10.out

Please make sure rec.pdb and lig.pdb files are available in your Colab env.