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.
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:
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:
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