Openbable Issue

[smaitychemlab-art]

2.4 version is not compatable with new Ubuntu or Linux mint. can i use babel 3?

[GHeinzelmann]

Hi, and thanks for your interest in the BAT code. I did not know about this 2.4 version incompatibility, thanks for letting me know. Openbabel 3 sometimes changes the ligand name to UNK, which produces an error later on in the workflow, that is why I avoid it. I doesn't always happen, but it will fail depending on the system. But I will look into this problem and fix it soon.

For now, if you face that bug in your system, you can just rename your ligand in the pdb file to UNK. Alternatively, you can use an already protonated ligand and set the retain_lig_prot variable to 'yes'. In the latter case, babel is not needed in the workflow.

[smaitychemlab-art]

Thanks for your kind reply. Meanwhile, I installed Openbable 2.4 inside the latest version of Linuxmint, the trick given bellow.
Download openbabel,extract inside the folder issue following codes.
mkdir build
cd build
cmake -DCMAKE_INSTALL_PREFIX=/usr/local -DOPENBABEL_USE_SYSTEM_INCHI=OFF ..
make -j30 #as i have 32cpus i deployed 30
make -j30 install

in the home folder it installed.

Requesting you to help me by providing the execution process.

I have 10ligands. one control ligand. for each of them i executed 250ns MD simulation using pmemd.cuda, as well for Apo protein. its NVT NPT ensambled MD, Cut off 0.8, Amber 14sb ff, and Gaff2 ff for ligand respectively. The MD descriptors indicates the system well eqilibrated at ~200+ns, so i did not extend the simulation time . In addition MMGBSA.py script assisted MMGBSA depict high negetive score of all 10 ligands compare to control ligand.

I want to calculate Relative binding free energy using BAT pay. I dont have access to your full paper. I explored the documentation. but unable to execute bat.py for my system. it will be nice if u kindly guide me how to execute BAT.py for my system step by step it will be helpful to select acceptable ligand for wet lab synthesis and biological evaluation. Thanks for your kind attention.
regards
Maity.s

[GHeinzelmann]

Sure, do you need to set up a new protein system with BAT.py? Have you ran into any errors when following the guidelines in the User Guide? Best,

Germano

[smaitychemlab-art]

yes i need to set up brand new protein system with BAT.Py.

when i executed the BAT.Py from parent folder with given folder structure it returns following infos
base) soumya@soumya:/BAT_py-master/BAT$ python BAT.py
Use the flags -i and -s for the input file and current stage of the calculations
Example: python BAT.py -i input.in -s equil
(base) soumya@soumya:/BAT_py-master/BAT$ python BAT.py -i input-amber-rank.in -s out.log
Receptor/complex structures:
receptor-5uf0
Ligand names
['89J', '89G', '87D', '0S6', '88M']
Cobinders names:
[]
lambda values: [0.009219682876640378, 0.0479413718147626, 0.11504866290284765, 0.20634102285669126, 0.31608425050090994, 0.43738329574426554, 0.5626167042557344, 0.6839157494990901, 0.7936589771433087, 0.8849513370971523, 0.9520586281852375, 0.9907803171233596]
Gaussian weights: [0.023587668193255706, 0.05346966299765953, 0.08003916427167321, 0.10158371336153287, 0.1167462682691773, 0.12457352290670134, 0.12457352290670134, 0.1167462682691773, 0.10158371336153287, 0.08003916427167321, 0.05346966299765953, 0.023587668193255706]
(base) soumya@soumya:~/BAT_py-master/BAT$

i am requesting you, if u kindly provide step by step protocol to execute ABFE and RBFe in workstation, without slurm

1. List of nput files required
   2, which scripts I need to use for pre and post calculation with what type of flags?
   3.. which parameters in which file i should edit or modify
2. shall i need to use pre MD simulation files like out put of NPT/NVT equilibrated files or post MD last frame ?
   5 How to get Del G,PMF to calculate kd

shall i need to declare paths of openbabel 2,4 installation path via bashrc? Thanks

[debanjansen48]

in my system it says unable to import build from lib ?

[GHeinzelmann]

Hi. It seems that your equilibration step ran correctly, so you should now see an ./equil folder, and inside it one folder for each of the ligands. The bash scripts to run the equilibration simulations without SLURMM are inside these ligand folders, and they are called run-local.bash. Just execute them and if the needed programs (AMBER pmemd.cuda or OpenMM) are in your path, the simulations should run normally.

No need for babel at this stage, only for the parameter generation step. After the equilibration simulations are finished for all ligands, you can then run the free energy (fe) step, as explained in the tutorial. The relation between Kd and the calculated binding free energy is exponential, and you can find it in reference 1 from the tutorial (Eq. 2 of this paper).

[smaitychemlab-art]

Hi Sir, thanks I foud it its running
BAT/equil/lig-5ueu$ bash run-local.bash
0
Note: The following floating-point exceptions are signalling: IEEE_UNDERFLOW_FLAG IEEE_DENORMAL
0
Note: The following floating-point exceptions are signalling: IEEE_UNDERFLOW_FLAG IEEE_DENORMAL
0
Note: The following floating-point exceptions are signalling: IEEE_UNDERFLOW_FLAG IEEE_DENORMAL
0
Note: The following floating-point exceptions are signalling: IEEE_UNDERFLOW_FLAG IEEE_DENORMAL
0
Note: The following floating-point exceptions are signalling: IEEE_UNDERFLOW_FLAG IEEE_DENORMAL
0
Note: The following floating-point exceptions are signalling: IEEE_UNDERFLOW_FLAG IEEE_DENORMAL
0
Note: The following floating-point exceptions are signalling: IEEE_UNDERFLOW_FLAG IEEE_DENORMAL
0
Note: The following floating-point exceptions are signalling: IEEE_UNDERFLOW_FLAG IEEE_DENORMAL
0
Note: The following floating-point exceptions are signalling: IEEE_UNDERFLOW_FLAG IEEE_DENORMAL
pmemd.cuda -O -i mdin-01 -p full.hmr.prmtop -c md00.rst7 -o md-01.out -r md01.rst7 -x md-01.nc -ref full.inpcrd
0
So, i need to enter into individual lig folders and issue the command bash/run-local.bash. I think it is not generating any log file or info file.

[GHeinzelmann]

OK it seems that everything went well, the output files are the *.out and *.nc ones, the latter being the trajectories. Do that for every ligand, and after all simulations are finished run the BAT.py fe step as explained in the tutorial.

[smaitychemlab-art]

I executed individual Simulations now it returns error during analysis. I think for my system i need to adjust some parameters and need to use some alignment job. However I am learning it using the tutorial. the error i am encountered with described bellow. (Sorry for my bad English, I am not a native English speaker, apology ).
(base) soumya@soumya:/Documents/BAT.py-master/BAT$ python BAT.py -i input-amber-rank.in -s analysis
Receptor/complex structures:
receptor-5uf0
Ligand names
['89J', '89G', '87D', '0S6', '88M']
Cobinders names:
[]
lambda values: [0.009219682876640378, 0.0479413718147626, 0.11504866290284765, 0.20634102285669126, 0.31608425050090994, 0.43738329574426554, 0.5626167042557344, 0.6839157494990901, 0.7936589771433087, 0.8849513370971523, 0.9520586281852375, 0.9907803171233596]
Gaussian weights: [0.023587668193255706, 0.05346966299765953, 0.08003916427167321, 0.10158371336153287, 0.1167462682691773, 0.12457352290670134, 0.12457352290670134, 0.1167462682691773, 0.10158371336153287, 0.08003916427167321, 0.05346966299765953, 0.023587668193255706]
Traceback (most recent call last):
File "/home/soumya/Documents/BAT.py-master/BAT/BAT.py", line 1070, in
analysis.fe_values(blocks, components, temperature, pose, attach_rest, lambdas, weights, dec_int, dec_method, rest, dic_steps1, dic_steps2, dt)
~~~~~~~~~~~~~~~~~~^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
File "/home/soumya/Documents/BAT.py-master/BAT/lib/analysis.py", line 666, in fe_values
with open("restraints.dat", "r") as fin:
~~~~^^^^^^^^^^^^^^^^^^^^^^^
FileNotFoundError: [Errno 2] No such file or directory: 'restraints.dat'
(base) soumya@soumya:/Documents/BAT.py-master/BAT$

However for a brand new protein ligand system What ever i understood I prepared a protocol for your consideration. Attached with this message.
Thanks

BAT_RBFE_Protocol.docx

[GHeinzelmann]

Hi. Did you run all the free energy simulations using the run-express.bash script, after running the fe step?

[smaitychemlab-art]

i tried to execute run-express.bash script from run_file folder it returns error, as well i tried to execute it from BAT folder as well from individual ligand folder but encountered with error. Instead i executed following commands and return error.

soumya@soumya:/Documents/BAT.py-master/BAT$ python BAT.py -i input-amber-rank.in -s run_files
Receptor/complex structures:
receptor-5uf0
Ligand names
['89J', '89G', '87D', '0S6', '88M']
Cobinders names:
[]
lambda values: [0.009219682876640378, 0.0479413718147626, 0.11504866290284765, 0.20634102285669126, 0.31608425050090994, 0.43738329574426554, 0.5626167042557344, 0.6839157494990901, 0.7936589771433087, 0.8849513370971523, 0.9520586281852375, 0.9907803171233596]
Gaussian weights: [0.023587668193255706, 0.05346966299765953, 0.08003916427167321, 0.10158371336153287, 0.1167462682691773, 0.12457352290670134, 0.12457352290670134, 0.1167462682691773, 0.10158371336153287, 0.08003916427167321, 0.05346966299765953, 0.023587668193255706]
(base) soumya@soumya:/Documents/BAT.py-master/BAT$ python BAT.py -i input-amber-rank.in -s fe
Receptor/complex structures:
receptor-5uf0
Ligand names
['89J', '89G', '87D', '0S6', '88M']
Cobinders names:
[]
lambda values: [0.009219682876640378, 0.0479413718147626, 0.11504866290284765, 0.20634102285669126, 0.31608425050090994, 0.43738329574426554, 0.5626167042557344, 0.6839157494990901, 0.7936589771433087, 0.8849513370971523, 0.9520586281852375, 0.9907803171233596]
Gaussian weights: [0.023587668193255706, 0.05346966299765953, 0.08003916427167321, 0.10158371336153287, 0.1167462682691773, 0.12457352290670134, 0.12457352290670134, 0.1167462682691773, 0.10158371336153287, 0.08003916427167321, 0.05346966299765953, 0.023587668193255706]
Setting up lig-5uf0
window: m00 weight: 0.0
Traceback (most recent call last):
File "/home/soumya/Documents/BAT.py-master/BAT/BAT.py", line 1026, in
anch = build.build_dec(fwin, hmr, mol, pose, molr, poser, comp, win, water_model, ntpr, ntwr, ntwe, ntwx, cut, gamma_ln, barostat, receptor_ff, ligand_ff, dt, sdr_dist, dec_method, l1_x, l1_y, l1_z, l1_range, min_adis, max_adis, ion_def, other_mol, solv_shell)
File "/home/soumya/Documents/BAT.py-master/BAT/lib/build.py", line 1094, in build_dec
shutil.copy(file, './')
~~~~~~~~~~~^^^^^^^^^^^^
File "/home/soumya/miniconda3/lib/python3.13/shutil.py", line 428, in copy
copyfile(src, dst, follow_symlinks=follow_symlinks)
~~~~~~~~^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
File "/home/soumya/miniconda3/lib/python3.13/shutil.py", line 240, in copyfile
raise SameFileError("{!r} and {!r} are the same file".format(src, dst))
shutil.SameFileError: '../m00/build-dry.pdb' and './build-dry.pdb' are the same file
(base) soumya@soumya:~/Documents/BAT.py-master/BAT$

[GHeinzelmann]

Hi. This seems easy to address, can you contact me through the email given in the end of the tutorial? That way I can check your files if needed. Thanks.