Covalent docking
================

this is all about covalent docking. This section covers advanced usage scenarios and methodologies for further refining and enhancing the outcomes of your docking campaigns.

.. toctree::
   :maxdepth: 2



Covalent docking
------------------------------

General notes
+++++++++++++++++

*  First optimize grids with the set of non-covalent ligands and decoys
*  check poses after covalent docking
*  scores do not mean much, set `mol2_score_maximum` to +10, sometimes even +20
*  IFP with the distance filter (use Van der Waals) 

Preparing ligands
++++++++++++++++++++++

Prepare “SMILES ID” file.
``ssh n-1-17`` (or another development node)
Source environment with RDkit
``source /nfs/home/ak87/miniconda3/etc/profile.d/conda.sh``
``conda activate py3.11``
``python ~ak87/PROGRAM/convert_smiles_to_covalent.py ald bbv-cov-ald.smi bbv-cov-ald-test.smi``
This script enumerates all stereoisomers and converts SMILES to the covalent ones. Currently, only conversions for aldehydes and nitriles is supported. Usage: 
First arg:    ald or nitr for aldehyde or nitrile
Second arg:    input smi file
Third arg:    output file name

**Building Aldehydes and Ketones:**

.. code:: bash

   source ~elisfink/.csh_corina
   sh ~elisfink/scripts/09-2022-ligbuild/0001_wrapper_queue_build_smiles_ligand_mod_corina_covalent.csh input.smi

To get SDI from these built molecules:

``ls $PWD/{smi file without .smi}/sge*/finished//.db2.gz > built_ligands.sdi``

**Building Nitriles:**

.. code:: bash

   source ~elisfink/.csh_corina
   csh ~elisfink/scripts/09-2022-ligbuild/0001_wrapper_queue_build_smiles_ligand_mod_corina_covalent_permissive.csh input.smi

To get SDI from these built molecules:

``ls $PWD/{smi file without .smi}/sge*/finished//.db2.gz > built_ligands.sdi``


Ready libraries
++++++++++++++++++++++

**Nitriles**

This doesn't exist anymore (lost to ex9 outage?):
``/mnt/nfs/ex9/work/xiaobo/20200303-COVID-19-mainprotease-lib/Jack-suggested-warheads/nitrile/nitriles_leads_xiaobo-all.lib``

This doesn't exist anymore (lost to ex9 outage?):
``/mnt/nfs/ex9/work/sgu/corona/lsd/nitriles_hid/nitriles.lib``

``/mnt/nfs/exa/work/elisfink/covalent_lib/nitriles/build_03282020/nitriles_elissa.lib``

They should be leadlike 250-350MW ~10M

**~17M acrylamides**

Wynton location:

``/wynton/group/bks/covalent/acrylamides/lib_elissa_2021/wynton_acrylamides_lib2021.sdi``

Gimel location:

``/mnt/nfs/exa/work/elisfink/covalent_lib/acrylamides/search_03022021/build/acrylamides_050621.list``

**Expanded aldehyde library**

Found ~5M in searching the larger enamine databases, there might be some overlap with the 2020 subset that was originally around 2M. Wynton location for 2021 subset (found in 2021 for Nsp14 project):

``/wynton/group/bks/covalent/aldehydes/lib_elissa_2021.txt`` 

Gimel 2020 subset:

``/mnt/nfs/exa/work/elisfink/covalent_lib/build_aldehydes/final_library/aldehydes_list``

Gimel 2021 subset:

``/nfs/home/elisfink/exa/covalent_lib/aldehydes/search_03012021/build/lib_elissa_2021.txt``