Problems with generating the combinatorial pharmacophore library

[josegomide]

Dear David,

I hope this message finds you well.

I am encountering problems while generating the combinatorial pharmacophore library. I have successfully acquired the super_pharmacophore.pml file using the trajectory_pharmacophore_combo.cfg and analyzed the pharmacophore features with LigandScout (the image bellow represents the pharmacophore points selected after the ligandscout analysis. 16 points in total):

However, when I run the command pyrod library.cfg, I receive the following message:

"(pyrod) lammol@lammol:~/pyrod/nsp2$ pyrod library.cfg /home/lammol/miniconda3/envs/pyrod/lib/python3.8/site-packages/Bio/Application/init.py:40: BiopythonDeprecationWarning: The Bio.Application modules and modules relying on it have been deprecated. Due to the ongoing maintenance burden of keeping command line application wrappers up to date, we have decided to deprecate and eventually remove these modules. We instead now recommend building your command line and invoking it directly with the subprocess module. warnings.warn(

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                                                                 ~~~\   oo  oo  oo  oo  /~~~                                                                     
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                                                                     ~~    PyRod v0.7.5     ~~~                                                                          
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                                                                  Tracing water molecules in molecular dynamics simulations.                                                                              

Starting library generation. The given pharmacophore contains incomplete hydrogen bonding features. Feature type is hd2 but only one interaction partner was found. Either create a new pharmacophore without splitting ha2, hd2 and hda features or set pyrod pharmacophore to false."

I noticed that the super_pharmacophore obtained by the trajectory_pharmacophore_combo.cfg did not return any acceptor points, making it impossible to create a new pharmacophore without splitting the ha2, hd2, and hda features. The only option left was to set the pharmacophore option to false, but, after modifying it, pyrod library.cfg returned:

"(pyrod) lammol@lammol:~/pyrod/nsp2$ pyrod library.cfg /home/lammol/miniconda3/envs/pyrod/lib/python3.8/site-packages/Bio/Application/init.py:40: BiopythonDeprecationWarning: The Bio.Application modules and modules relying on it have been deprecated. Due to the ongoing maintenance burden of keeping command line application wrappers up to date, we have decided to deprecate and eventually remove these modules. We instead now recommend building your command line and invoking it directly with the subprocess module. warnings.warn(

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                                                                                   )__)                                                                                      
                                                                              ))  )__) ))                                                                                  
                                                                             )_) )_)))                                                                                 
                                                                        _    )_)_))_)                                                                                
                                                                         \---_|_/|_|_-----                                                                           
                                                                 ~~~\   oo  oo  oo  oo  /~~~                                                                     
                                                                   ~~~~~~     ~~    ~~                                                                       
                                                                     ~~    PyRod v0.7.5     ~~~                                                                          
                                                                            ~~     ~    ~~~                                                                              
                                                                  Tracing water molecules in molecular dynamics simulations.                                                                              

Starting library generation. 0 pharmacophores will be written, taking about 0 B of space." As a result, the library.cfg file does not produce any output containing the combinatorial pharmacophore library. The only file generated is template_pharmacophore.pml, which is identical to the input pharmacophore file processed after the LigandScout analysis.

Could you please advise why this is happening and how I might resolve this issue?

Thank you for your time and assistance.

Best regards, José Gomide