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GVSrun
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#!/bin/bash
#########################################################################
# GVSrun, Version 1.4.8
# 2021, ShanghaiTech University, Wang Lin
# Email: [email protected]
#########################################################################
# Defulat
#Database
if [ ! ${compound_library} ];then
echo "Warning: The GVSrun need a \$compound_library environmental variable, or you can use -d to specify a library."
fi
Database_Path=${compound_library}
for i in `ls ${Database_Path}`;do
Database_list=`echo "${Database_list}${i} "`
done
#Host and Schrodinger Path
HOST=CPU
Njobs=100
SCHRODINGER=${SCHRODINGER}
Prime=10
Glide=90
LigPrep=30
Phase=10
Qsite=10
QIKPROP=10
MACROMODEL=10
#INPUT
input=None
Running_Mode="Fast"
Database="Custom_DB"
#Setting
PH=7.0:2.0
Dock_out_conf=1
HTVS_out_num="5%"
Docking_out_num="4000"
SET_PULL_NUM="500"
QM_set="B3LYP-D3(BJ):6-311G**"
MW_range="100:400"
scalingVdW=0.8
#Ligand Filter
Ligand_Filter=true
FilterReactivegroup=false
#Docking
corse_ff="OPLS_2005"
Force_Field="OPLS4"
#Shape Screening
keep_num=10000
shape_sample_method=rapid
max_confs=100
shape_screen_default="${keep_num}:${shape_sample_method}:${max_confs}"
shape_screen_Array=(${shape_screen_default//:/ })
shape_screen_swith=false
function options(){
cat << EOF
These options are supported by this script.
-m Running Mode: <Fast>
Running Mode means a serial combination of different computing tasks.
@Available Running Mode:
Fast: Fast Virtual Screening.
"HTVS_Normal+SP_Normal"
Normal: Filter The Drug-like compounds and dock screening.
"RDL+HTVS_Normal+QIKPROP+R5R+SP_ExtensionA"
Local: Local docking and screening were carried out using the input ligand structure.
"SP_local+MMGBSA_OPT"
Reference: Virtual Screening with reference ligand restrain.
"HTVS_REF+SP_REF+QIKPROP+R5R"
Prep_Normal: Virtual Screening for un-prepared compounds database.
"No_Dup+RDL+IONIZE+HTVS_Normal+QIKPROP+R5R+SP_ExtensionA"
Normal_MMGBSA: Virtual Screening and MMGBSA re-scoring.
"RDL+HTVS_Normal+QIKPROP+R5R+SP_ExtensionA+MMGBSA_EN"
Cov_Screening: Virtual Screening to discover covalent durg.
"R+HTVS_Normal+SP_ExtensionA+SP_Enhanced"
Induce_Fit_Screening: Induce fit screening.
"IFT_pre+IFT"
QM_Screening: Virtual Screening and QMMM re-docking.
"RDL+HTVS_Normal+QIKPROP+R5R+SP_ExtensionA+QM_redock+RMSD"
Advance: dock screening.
"HTVS_Normal+SP_ExtensionA+SP_Enhanced"
Shape_Screening: perform screening based on reference ligand shape.
"PhaseShape+SP_local"
LocalShape_Screening: perform screening based on reference ligand shape.
"localShape+SP_local"
Advance_Shape_Screening: perform screening based on reference ligand shape.
"HTVS_Shape+SP_Shape"
or Custom Running Mode, e.g. -m "EDL+R+HTVS+CD"
Task List as followed:
@LigFilter: Some chemical properties were used to filter the molecules in the library.
Such as, Molecule Weight, Number of Rings, cLogP.
RDL: Rough Drug Like, MW<=650/Num_rotatable_bonds<=10/Num_rings<=6, Do not need QIKPROP.
EDL: Exact Drug Like, MW<=350/Num_rotatable_bonds<=8/Num_rings<=4, Do not need QIKPROP.
Fragment: Small Fragment Molecule, Num_heavy_atoms<=15, Do not need QIKPROP.
R:reactive, virtual screening will perform with only reactive compounds! Do not need QIKPROP.
if you do not know what this option is talking about, use it with caution.
NR:Non_reactive, remove reactive compounds from the compound library, Do not need QIKPROP.
Warhead_SO: Only covalent compounds similar to known drugs were retained. Covalent to Cys or Ser.
Warhead_N: Only covalent compounds similar to known drugs were retained. Covalent to Lys.
NPSE: Non_Phosphonate_esters and Sulphonate_esters, Do not need QIKPROP.
No_Dup: removes duplicate variants by SMILES strings.
QIKPROP: Calculate cLogP, PSA, SASA, QPlogPo/w, QPlogHERG, QPPCaco, ...
5R: Standard LIPINSKI 5 Rule, need QIKPROP.
R5R: Rough 5 Rule, need QIKPROP.
Oral: Retain compounds with Oral Absorption, need QIKPROP.
3R: Jorgensen's rule of three, orally available, need QIKPROP.
Star: Retain compounds similar to known drugs, need QIKPROP.
Oral_Drug: Combine 3R and 5R but allow one dissatisfy term.
BBB: Filter for Blood-brain barrier, need QIKPROP.
MW: Filter compounds by Molecular weight, need -W option.
PosMol: retain the positively charged compounds.
NegMol: retain the negatively charged compounds.
@LigPrep: Use LigPrep to prepare filtered structures. Related to -r option.
IONIZE: Generate ionization states when using Ionizer.
EPIK4: Use Epik for generating ionization and tautomeric states.
EPIK32: Use Epik for generating ionization and tautomeric states.
RS1: SampleRings, and output 2 conformer in 300 iterations.
RS4: SampleRings, and output 8 conformer in 500 iterations.
RS_Fast: SampleRings, and output 2 conformer in 100 iterations.
CONFGEN: Preform ConfSearch by macromodel, with User defined force field.
CONFGEN_Fast: Preform ConfSearch fastly by macromodel, with User defined force field.
MMFF_CONFGEN: Preform ConfSearch by macromodel, MMFFs force field.
Combine_CONFGEN: Preform ConfSearch with two user defined force field and MMFFs.
@Screening: Reduce the number of compounds rough docking. Related to -a option.
localShape: Shape Screening using external app, taken together with the local mode!
NOTE: Must be the first in the pipeline.
PhaseShape: Shape Screening in pipeline.
HTVS_Normal: The standard HTVS screening.
HTVS_Rough: The reduced HTVS screening, The sample size is reduced to nearly half of the HTVS_Normal.
HTVS_Fragment: It is suitable for rapid screening of compound fragments.
HTVS_REF: The standard HTVS screening based on a template ligand, This will significantly increase the hit rate.
IFT_pre: Pre-screening for Induce fit docking, also useful for screening before Covalent Docking.
NOTE: Set RECEP_VSCALE to 0.50 in Grid Geneation is a good idea.
HTVS_Shape: Docking with reference ligand shape. with -R and -E option.
@Standard_Docking: Standard docking was performed to rank the compounds. Related to -b and -c option.
SP_Normal: The standard SP docking.
SP_ExtensionA: Reward intramolecular ligand hydrogen bonds, and accept halogens as H-bond acceptors.
SP_ExtensionB: Besides 'ExtensionA', also Accept aromatic hydrogens(>0.15) as potential H-bond donors.
SP_REF: The standard SP docking based on a template ligand, This will significantly increase the hit rate.
SP_Fragment: It is suitable for docking and scoring of compound fragments.
SP_Enhanced: Increase the depth of sampling for larger grid or More accurate poses.
SP_local: Docking is performed using the initial coordinates of the ligand,
which is usually used as a post-processing for pharmacophore screening.
SP_Shape: Docking with reference ligand shape. with -R and -E option.
XP_Normal: The standard XP docking.
XP_ExtensionA: Reward intramolecular ligand hydrogen bonds, and accept halogens as H-bond acceptors.
XP_ExtensionB: Besides 'ExtensionA', also Accept aromatic hydrogens(>0.15) as potential H-bond donors.
XP_REF: The standard XP docking based on a template ligand, This will significantly increase the hit rate.
XP_Fragment: It is suitable for docking and scoring of compound fragments.
XP_Enhanced: Increase the depth of sampling for larger grid orMore accurate poses.
XP_local: Docking is performed using the initial coordinates of the ligand,
which is usually used as a post-processing for pharmacophore screening.
@Ligand Clustering: 2D similarity clustering.
The format of this task is "FingerprintType_SimilarityMetric", such as MolPrint2D_Soergel, Topo_Tanimoto.
Currently, those task was been supproted:
FingerprintType: Linear, Radial, MolPrint2D, Topo, Dendritic;
SimilarityMetric: Tanimoto, Euclidean, Cosine, Soergel.
# Tanimoto Metric is the industry standard.
# Radial, dendritic, or MolPrint2D often give the best results.
@Advanced_Docking: Advanced docking to generate Induce-Fited/Covalent complex structures.
!NOTE: The Advanced_Docking Taskes can only receive a small number of ligands (< 200 ~ 2000).
IFT: Induce Fit Refinement.
CD: Covalent Docking to ser, cys or lys. Depend on the -C option.
Contains Michael_Addition, Epoxide_Opening, and Conjugate_Addition, for cys or ser.
Contains Imine Condensation and [C]=[C]-[S](=O)(=O), for lys.
QMMM: Perform QM/MM optimization.
QM_redock: Perform SP docking use charge from QMMM.
MMGBSA_EN: Perform MM-GBSA calculation. Do Not refine the structure.
MMGBSA_MIN: Perform MM-GBSA calculation. In Minimization Mode.
MMGBSA_OPT: Perform MM-GBSA calculation. In Side chain repack Mode.
@RMSD: Calculate RMSD between the previous stage with earlier stages.
Thank you for your using, If you found any problem, Please contact [email protected].
EOF
}
function help(){
cat<<HELP
Perform Virtual Screening Workflow.
Usage: GVSrun [OPTION] <parameter>
Input parameter:
-i Grid file input.
Use a file name (Multiple files are wrapped in "", and split by ' ') or regular expression to represent your input Grid file, default is *.zip.
-D Which databases do you want to screen? The Database basic path is <$Database_Path>.
These database are Supported:
HELP
ls -w 150 ${Database_Path} # echo "${Database_list}"
cat<<HELP
-d Provide your own database path, the compounds files are recommended as maegz or SDF file format.
-R Optional, reference Ligands correlated with the grid or use for RMSD calculation.
As *.mae, *.maegz (for query structure) or *.phypo (for pharmacophore hypothesis).
-m Running Mode: a serial combination of different computing tasks.
Show all mode and task in this option using "-O".
@ Available Running Mode: <Fast>
Fast: Fast Virtual Screening.
Normal: Filter The Drug-like compounds and dock screening.
Reference: Virtual Screening with reference ligand restrain.
Prep_Normal: Virtual Screening for un-prepared compounds database.
*Normal_MMGBSA: Virtual Screening and MMGBSA re-scoring.
*Cov_Screening: Virtual Screening to discover covalent durg.
*Induce_Fit_Screening: Induce fit screening.
*QM_Screening: Virtual Screening and QMMM re-docking.
Local: Local docking and screening were carried out using the input ligand structure.
Shape_Screening: perform screening based on reference ligand shape.
Advance: advance docking screening.
Advance_Shape_Screening: perform screening based on reference ligand shape.
GeminiMol_Advance: perform advance docking screening with GeminiMol output.
@ or Custom Running Mode, e.g. -m "EDL+R+HTVS+CD"
Control parameters:
-F Force Fields for docking stage (SP/XP/MMGBSA...), OPLS_2005, OPLS3e or OPLS4. <OPLS4>
-f Force Fields for other stage (HTVS/LigPrep...), OPLS_2005, OPLS3e or OPLS4. <OPLS_2005>
-W Define a Max/Min Molecular weight for MW module, such as "100:400" <100:400>
-T Set a Job Name. Default is "Grid_name-Database_name-Run_Mode".
-C Aattach residue number on receptor, required in Covalent Docking.
e.g. "cys:A:1425", the A is chain name and 145 is the atom number(Heavy atom).
The cys is residue name for A:1425, Supported residues: cys, ser, lys.
-q Define a "DFT:Basis_Set" to QM/QMMM, default is "B3LYP-D3(BJ):6-311G**".
Other QM setting: "B3LYP-D3M(BJ):6-311G+**","M06‑2X:def2-tzvpp(-g)","wB97M‑V:cc-pVTZ-pp"
-p set a PH:PHT for ligPrep, default is 7.0:2.0, means 7.0±2.0. <7.0:2.0>
-s Set a SMARTs Expression for compounds filter at first step. such as [B]([O])[O].
-E Shape Screening Options. <${shape_screen_default}>
The paramter means: "keep_num:shape_sample_method:max_confs";
-v scalingVdW for ligand, used in conjunction with prime MMGBSA to induce fit refinement. 0.8 is OK. <${scalingVdW}>
OUTPUT parameters:
-a The number of Output compounds per Screening Task. <5%>
e.g. 10% means retain top 10% compounds.
10000 means retain top 10000 compounds.
-b The number of Output compounds after Standard docking Task. <4000>
-c The number of conformations generated by each ligand in the docking task. <1>
-e The number of candidates to IFT/CD/MMGBSA/QMMM. <500>
Job control:
-H Host Name of your Queue, defult is ${HOST}.
-N The max number of subjobs. <100>
-G The number of Glide subjobs. <90>
-P The number of Prime subjobs. <10>
-L The number of LigPrep subjobs. <30>
-A The number of phase subjobs. <10>
-Q The number of Qsite subjobs. <10>
-K The number of QIKPROP subjobs. <10>
-M The number of MACROMODEL subjobs. <10>
-S Your Schrodinger path. <$SCHRODINGER>
Thank you for your using, If you found any problem, Please contact [email protected].
HELP
}
while getopts ":hOi:D:d:m:T:R:a:e:C:b:p:q:c:H:N:P:G:L:A:Q:K:M:S:F:f:W:E:v:" opt
do
case $opt in
h)
help
exit;;
O)
options
exit;;
i)
input=`readlink -f $OPTARG`;;
D)
Database=$OPTARG;;
d)
User_dbPath=`readlink -f $OPTARG`;;
m)
Running_Mode=$OPTARG;;
T)
Job_Title=$OPTARG;;
R)
Reference_Ligand=`readlink -f $OPTARG`;;
a)
HTVS_out_num=$OPTARG;;
e)
SET_PULL_NUM=$OPTARG;;
C)
covalent_attach_residue=$OPTARG;;
b)
Docking_out_num=$OPTARG;;
p)
PH=$OPTARG;;
s)
SMARTs=$OPTARG;;
q)
QM_set=$OPTARG;;
c)
Dock_out_conf=$OPTARG;;
H)
HOST=$OPTARG;;
N)
Njobs=$OPTARG;;
P)
Prime=$OPTARG;;
G)
Glide=$OPTARG;;
L)
LigPrep=$OPTARG;;
A)
Phase=$OPTARG;;
Q)
Qsite=$OPTARG;;
K)
QIKPROP=$OPTARG;;
M)
MACROMODEL=$OPTARG;;
S)
SCHRODINGER=$OPTARG;;
F)
Force_Field=$OPTARG;;
f)
corse_ff=$OPTARG;;
W)
MW_range=$OPTARG;;
E)
shape_screen_swith=true
shape_screen_Array=(${OPTARG//:/ });;
v)
scalingVdW=$OPTARG;;
?)
echo ""
echo "Error: Do not use undefined options."
echo ""
help
exit;;
esac
done
Parse_Running_Mode(){
# Parse_Running_Mode Running_Mode
Running_Mode=$1
if [ $Running_Mode == "Normal" ]; then
Pipeline="RDL+HTVS_Normal+QIKPROP+R5R+SP_ExtensionA"
elif [ $Running_Mode == "Prep_Normal" ]; then
Pipeline="No_Dup+RDL+IONIZE+HTVS_Normal+QIKPROP+R5R+SP_ExtensionA"
elif [ $Running_Mode == "Normal_MMGBSA" ]; then
Pipeline="RDL+HTVS_Normal+QIKPROP+R5R+SP_ExtensionA+MMGBSA_EN"
elif [ $Running_Mode == "Reference" ]; then
Pipeline="HTVS_REF+SP_REF+QIKPROP+R5R"
elif [ $Running_Mode == "Induce_Fit_Screening" ]; then
Pipeline="IFT_pre+IFT"
elif [ $Running_Mode == "Cov_Screening" ]; then
Pipeline="R+HTVS_Normal+SP_ExtensionA+SP_Enhanced"
elif [ $Running_Mode == "Fast" ]; then
Pipeline="HTVS_Normal+SP_Normal"
elif [ $Running_Mode == "QM_Screening" ]; then
Pipeline="RDL+HTVS_Normal+QIKPROP+R5R+SP_ExtensionA+QM_redock+RMSD"
elif [ $Running_Mode == "Shape_Screening" ];then
Pipeline="localShape+SP_local"
elif [ $Running_Mode == "Local" ];then
Pipeline="SP_local+MMGBSA_OPT"
elif [ $Running_Mode == "Advance" ];then
Pipeline="HTVS_Normal+SP_ExtensionA+SP_Enhanced"
elif [ $Running_Mode == "Advance_Shape_Screening" ];then
Pipeline="HTVS_Shape+SP_Shape"
elif [ $Running_Mode == "LocalShape_Screening" ];then
Pipeline="PhaseShape+SP_local"
elif [ $Running_Mode == "GeminiMol_Advance" ];then
Pipeline="No_Dup+RDL+EPIK4+HTVS_Normal+QIKPROP+R5R+SP_ExtensionA+SP_Enhanced"
else
Pipeline=$Running_Mode
Running_Mode="User_Defined"
fi
}
Params_check_and_report(){
Work_Dir=${PWD}
# Check SCHRODINGER and Host
if [ -d ${SCHRODINGER} ];then
if [ "${SCHRODINGER}" == "" ];then
echo "SCHRODINGER not found. Please check your SCHRODINGER Path."
exit
fi
if [ "`grep -c $HOST ${SCHRODINGER}/schrodinger.hosts`" == "0" ];then
echo $HOST "Host not found."
echo "These host are available:"
grep "^name" ${SCHRODINGER}/schrodinger.hosts | awk '{print $2}'
exit
fi
else
echo "SCHRODINGER not found. Please check your SCHRODINGER Path."
exit
fi
if [ ${User_dbPath} ];then
Database_Location=${User_dbPath}
else
if [ -d ${Database_Path}/${Database} ]; then
Database_Location=${Database_Path}/${Database}
elif [ -f ${Database_Path}/${Database} ]; then
Database_Location=${Database_Path}/${Database}
else
echo "Your compound database does not exist!"
echo "please check the script settings, or confirm the location of the database!"
exit
fi
fi
if [ $Reference_Ligand ];then
if [ -f ${Reference_Ligand} ]; then
if [ ${Reference_Ligand##*.} == "mae" ] || [ ${Reference_Ligand##*.} == "maegz" ] || [ ${Reference_Ligand##*.} == "sdf" ];then
Reference_Ligand_notice="Reference Ligand: ${Reference_Ligand}"
else
echo "The input reference ligand file must be *.mae, *.maegz or *.sdf!"
exit
fi
else
echo "Your reference ligand file is not exist or not a file!"
exit
fi
else
Reference_Ligand_notice="Reference Ligand: None"
fi
cat<<OUTPUTLOG
Virtual Screening Workflow Parameter:
Job Dir: ${Work_Dir}
Grid Files: ${input}
Database: ${Database_Location}
Running Mode: ${Running_Mode}
${Reference_Ligand_notice}
OUTPUTLOG
}
setGrid(){
cat<<GRID >> ${Inp_Name}
[SET:GRID]
VARCLASS Grid
FILE "${INPUT}"
GRID
}
setdatabase(){
if [ "${Database_Location: -5}"x == ".phdb"x ];then
cat<<SETDB >> ${Inp_Name}
[SET:INPUT_PhaseDB]
VARCLASS PhaseDB
PATH ${Database_Location}
[STAGE:DBexport]
STAGECLASS phase.DBExportStage
INPUTS INPUT_PhaseDB,
OUTPUTS INPUT_Ligands,
SETDB
elif [ ${Database_Location##*.} == "mae" ] || [ ${Database_Location##*.} == "maegz" ] || [ ${Database_Location##*.} == "sdf" ] || [ ${Database_Location##*.} == "smi" ];then
cat<<SETDB >> ${Inp_Name}
[SET:INPUT_Ligands]
VARCLASS Structures
FILES ${Database_Location},
SETDB
elif [ ${Database_Location##*.} == "csv" ];then
structconvert -smi SMILES -name ID $Database_Location ${Database_Location%.*}.sdf
cat<<SETDB >> ${Inp_Name}
[SET:INPUT_Ligands]
VARCLASS Structures
FILES ${Database_Location%.*}.sdf,
SETDB
elif [ -d ${Database_Location} ]; then
cat<<SETDB >> ${Inp_Name}
[SET:INPUT_Ligands]
SETDB
echo " VARCLASS Structures" >> ${Inp_Name}
echo -n " FILES " >> ${Inp_Name}
for file in `ls ${Database_Location}`;do
if [ ${file##*.} == "mae" ] || [ ${file##*.} == "maegz" ] || [ ${file##*.} == "sdf" ] || [ ${file##*.} == "smi" ];then
echo -n "${Database_Location}/${file}," >> ${Inp_Name}
else
echo "Warning: Your input ${Database_Location}/${file} is not recognized."
fi
done
echo "" >> ${Inp_Name}
else
echo "Your input ${Database_Location} is not recognized."
exit
fi
Ligand_name="INPUT_Ligands"
TO_RMSD="INPUT_Ligands"
}
SMARTs(){
cat<<Warhead >> ${Inp_Name}
[STAGE:SMARTs]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS SMARTs_OUT,
CONDITIONS "${SMARTs} >= 1"
Warhead
Ligand_name="SMARTs_OUT"
}
QIKPROP(){
cat<<QIKPROP >> ${Inp_Name}
[STAGE:PRE_QIKPROP]
STAGECLASS gencodes.RecombineStage
INPUTS ${Ligand_name},
OUTPUTS PRE_QIKPROP_RECOMBINE_OUT,
NUMOUT njobs
OUTFORMAT maegz
MIN_SUBJOB_STS 4000
MAX_SUBJOB_STS 40000
GENCODES YES
OUTCOMPOUNDFIELD s_vsw_compound_code
OUTVARIANTFIELD s_vsw_variant
UNIQUEFIELD s_m_title
[STAGE:QIKPROP]
STAGECLASS qikprop.QikPropStage
INPUTS PRE_QIKPROP_RECOMBINE_OUT,
OUTPUTS QIKPROP_OUT,
RECOMBINE YES
[USEROUTS:${task}]
USEROUTS QIKPROP_OUT,
STRUCTOUT QIKPROP_OUT
QIKPROP
Ligand_name="QIKPROP_OUT"
}
5R(){
cat<<5R >> ${Inp_Name}
[STAGE:5R]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS 5R_OUT,
CONDITIONS "r_qp_mol_MW <= 500", "r_qp_QPlogPo/w <= 5", "r_qp_donorHB <= 5", "r_qp_accptHB <= 10", "r_qp_PSA <= 120"
[USEROUTS:${task}]
USEROUTS 5R_OUT,
STRUCTOUT 5R_OUT
5R
Ligand_name="5R_OUT"
}
BBB(){
cat<<BBB >> ${Inp_Name}
[STAGE:BBB]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS BBB_OUT,
CONDITIONS "Num_rotatable_bonds <= 8", "r_qp_QPlogBB >= -3.0 AND <= 1.2", "r_qp_QPPMDCK >= 25"
[USEROUTS:${task}]
USEROUTS BBB_OUT,
STRUCTOUT BBB_OUT
BBB
Ligand_name="BBB_OUT"
}
3R(){
cat<<3R >> ${Inp_Name}
[STAGE:3R]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS 3R_OUT,
CONDITIONS "r_qp_QPlogS > -5.7", "r_qp_QPPCaco > 22", "r_qp_accptHB <= 10", "r_qp_#metab < 7"
[USEROUTS:${task}]
USEROUTS 3R_OUT,
STRUCTOUT 3R_OUT
3R
Ligand_name="3R_OUT"
}
R5R(){
cat<<R5R >> ${Inp_Name}
[STAGE:R5R]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS R5R_OUT,
CONDITIONS "r_qp_mol_MW <= 650", "r_qp_QPlogPo/w <= 7", "r_qp_donorHB <= 6", "r_qp_accptHB <= 20"
[USEROUTS:${task}]
USEROUTS R5R_OUT,
STRUCTOUT R5R_OUT
R5R
Ligand_name="R5R_OUT"
}
Star(){
cat<<Star >> ${Inp_Name}
[STAGE:Star]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS Star_OUT,
CONDITIONS "r_qp_#Star <= 5"
[USEROUTS:${task}]
USEROUTS Star_OUT,
STRUCTOUT Star_OUT
Star
Ligand_name="Star_OUT"
}
Oral(){
cat<<Oral >> ${Inp_Name}
[STAGE:Oral]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS Oral_OUT,
CONDITIONS "r_qp_HumanOralAbsorption >= 2"
[USEROUTS:${task}]
USEROUTS Oral_OUT,
STRUCTOUT Oral_OUT
Oral
Ligand_name="Oral_OUT"
}
Oral_Drug(){
cat<<Oral_Drug >> ${Inp_Name}
[STAGE:Oral_Drug]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS Oral_Drug_OUT,
CONDITIONS "r_qp_RuleOfFive < 2", "r_qp_RuleOfThree < 2"
[USEROUTS:${task}]
USEROUTS Oral_Drug_OUT,
STRUCTOUT Oral_Drug_OUT
Oral_Drug
Ligand_name="Oral_Drug_OUT"
}
EDL(){
cat<<EDL >> ${Inp_Name}
[STAGE:EDL]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS EDL_OUT,
CONDITIONS "Molecular_weight <= 350", "Num_rotatable_bonds <= 8", "Num_rings <= 4"
EDL
Ligand_name="EDL_OUT"
}
RDL(){
cat<<RDL >> ${Inp_Name}
[STAGE:RDL]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS RDL_OUT,
CONDITIONS "Molecular_weight <= 650", "Num_rotatable_bonds <= 10", "Num_rings <= 6"
RDL
Ligand_name="RDL_OUT"
}
PosMol(){
cat<<RDL >> ${Inp_Name}
[STAGE:PosMol]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS PosMol_OUT,
CONDITIONS "Total_charge > 0"
RDL
Ligand_name="PosMol_OUT"
}
NegMol(){
cat<<RDL >> ${Inp_Name}
[STAGE:NegMol]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS NegMol_OUT,
CONDITIONS "Total_charge < 0"
RDL
Ligand_name="NegMol_OUT"
}
Fragment(){
cat<<Fragment >> ${Inp_Name}
[STAGE:Fragment]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS Fragment_OUT,
CONDITIONS "Num_heavy_atoms <= 15"
Fragment
Ligand_name="Fragment_OUT"
}
R(){
cat<<RR >> ${Inp_Name}
[STAGE:RR]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS R_OUT,
CONDITIONS "Reactive_groups > 0"
RR
Ligand_name="R_OUT"
}
NR(){
cat<<NR >> ${Inp_Name}
[STAGE:NR]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS NR_OUT,
CONDITIONS "Reactive_groups == 0"
NR
Ligand_name="NR_OUT"
}
NPSE(){
cat<<NPSE >> ${Inp_Name}
[STAGE:NPSE]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS NPSE_OUT,
CONDITIONS "Phosphonate_esters == 0", "Sulphonate_esters == 0"
NPSE
Ligand_name="NPSE_OUT"
}
No_Dup(){
cat<<No_Dup >> ${Inp_Name}
[STAGE:No_Dup]
STAGECLASS filtering.MergeDuplicatesStage
INPUTS ${Ligand_name},
OUTPUTS No_Dup_OUT,
SMILES_FIELD VendorSMILES
DESALT YES
MERGE_PROPS YES
OUTFORMAT sdf
NEUTRALIZE YES
No_Dup
Ligand_name="No_Dup_OUT"
}
Warhead_SO(){
cat<<Warhead >> ${Inp_Name}
[STAGE:Warhead]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS Warhead_SO_OUT,
CONDITIONS "Michael_acceptors >= 1 OR [B]([O])[O] >= 1 OR [C;r3][O;r3][C;r3] >= 1 OR [S;X2;H1] >= 1 OR [C]#[N] >=1 OR [O-0X1]=[C]1[C][C][N]1 >= 1 OR [O]=[C,c]-[C,c]=[O] >=1 OR NC(=O)C(=O)C(C)N >= 1 OR [C,c]=[C,c]-[C,c]#[N,n] >= 1 OR [C-0X2]#[C-0X2][C-0X3]=[O-0X1] >= 1 OR [C][S][S][H] >= 1 OR [N]=[O,S] >= 1 OR [N]=[C]=[S] >= 1 OR [C;H1]([Cl])-[C](=[O]) >= 1 OR [C]=[C][c][n] >= 1"
[USEROUTS:${task}]
USEROUTS Warhead_OUT,
STRUCTOUT Warhead_OUT
Warhead
Ligand_name="Warhead_SO_OUT"
}
Warhead_N(){
cat<<Warhead >> ${Inp_Name}
[STAGE:Warhead]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS Warhead_N_OUT,
CONDITIONS "[C]=[C]-[S](=O)(=O) >= 1 OR [C](=[O])-[C] >= 1"
Warhead
Ligand_name="Warhead_N_OUT"
}
MW(){
MW_array=(${MW_range//:/ })
MW_min=${MW_array[0]}
MW_max=${MW_array[1]}
cat<<Warhead >> ${Inp_Name}
[STAGE:MW]
STAGECLASS filtering.LigFilterStage
INPUTS ${Ligand_name},
OUTPUTS MW_OUT,
CONDITIONS "Molecular_weight <= ${MW_max} AND >= ${MW_min}"
Warhead
Ligand_name="MW_OUT"
}
IONIZE(){
PH_array=(${PH//:/ })
PH_value=${PH_array[0]}
PHT=${PH_array[1]}
cat<<IONIZE >> ${Inp_Name}
[STAGE:IONIZE]
STAGECLASS ligprep.LigPrepStage
INPUTS ${Ligand_name},
OUTPUTS IONIZE_OUT,
RECOMBINE YES
MIXLIGS YES
SKIP_BAD_LIGANDS YES
UNIQUEFIELD s_m_title
OUTCOMPOUNDFIELD s_vsw_compound_code
USE_EPIK False
PH ${PH_value}
PHT ${PHT}
MAX_TAUTOMERS 4
NRINGCONFS 3
COMBINEOUTS YES
IONIZE YES
STEREO_SOURCE parities
NUM_STEREOISOMERS 16
MAX_STEREOISOMERS 8
REGULARIZE NO
[STAGE:POSTLIGPREP]
STAGECLASS ligprep.PostLigPrepStage
INPUTS IONIZE_OUT,
OUTPUTS LIGPREP_OUT,
UNIQUEFIELD s_vsw_compound_code
OUTVARIANTFIELD s_vsw_variant
PRESERVE_NJOBS YES
REMOVE_PENALIZED_STATES YES
[USEROUTS:${task}]
USEROUTS LIGPREP_OUT,
STRUCTOUT LIGPREP_OUT
IONIZE
Ligand_name="LIGPREP_OUT"
TO_RMSD="${Ligand_name}"
}
EPIK4(){
PH_array=(${PH//:/ })
PH_value=${PH_array[0]}
PHT=${PH_array[1]}
cat<<EPIK4 >> ${Inp_Name}
[STAGE:EPIK4]
STAGECLASS ligprep.LigPrepStage
INPUTS ${Ligand_name},
OUTPUTS EPIK4_OUT,
RECOMBINE YES
RETITLE YES
MIXLIGS YES
SKIP_BAD_LIGANDS YES
UNIQUEFIELD s_m_title
OUTCOMPOUNDFIELD s_vsw_compound_code
USE_EPIK YES
MAX_STATES 8
METAL_BINDING NO
PH ${PH_value}
PHT ${PHT}
MAX_TAUTOMERS 4
NRINGCONFS 4
COMBINEOUTS YES
STEREO_SOURCE parities
NUM_STEREOISOMERS 16
MAX_STEREOISOMERS 4
REGULARIZE NO
[STAGE:POSTLIGPREP]
STAGECLASS ligprep.PostLigPrepStage
INPUTS EPIK4_OUT,
OUTPUTS LIGPREP_OUT,
UNIQUEFIELD s_vsw_compound_code
OUTVARIANTFIELD s_vsw_variant
PRESERVE_NJOBS YES
REMOVE_PENALIZED_STATES YES
[USEROUTS:${task}]
USEROUTS LIGPREP_OUT,
STRUCTOUT LIGPREP_OUT
EPIK4
Ligand_name="LIGPREP_OUT"
TO_RMSD="${Ligand_name}"
}
EPIK32(){
PH_array=(${PH//:/ })
PH_value=${PH_array[0]}
PHT=${PH_array[1]}
cat<<EPIK32 >> ${Inp_Name}
[STAGE:EPIK32]
STAGECLASS ligprep.LigPrepStage
INPUTS ${Ligand_name},
OUTPUTS EPIK32_OUT,
RECOMBINE YES
RETITLE YES
MIXLIGS YES
SKIP_BAD_LIGANDS YES
UNIQUEFIELD s_m_title
OUTCOMPOUNDFIELD s_vsw_compound_code
USE_EPIK YES
MAX_STATES 64
METAL_BINDING YES
PH ${PH_value}
PHT ${PHT}
MAX_TAUTOMERS 16
NRINGCONFS 16
COMBINEOUTS YES
STEREO_SOURCE parities
NUM_STEREOISOMERS 64
MAX_STEREOISOMERS 32
REGULARIZE NO
[STAGE:POSTLIGPREP]
STAGECLASS ligprep.PostLigPrepStage
INPUTS EPIK32_OUT,
OUTPUTS LIGPREP_OUT,
UNIQUEFIELD s_vsw_compound_code
OUTVARIANTFIELD s_vsw_variant
MAXSTEREO 32
PRESERVE_NJOBS YES
REMOVE_PENALIZED_STATES YES
[USEROUTS:${task}]
USEROUTS LIGPREP_OUT,
STRUCTOUT LIGPREP_OUT
EPIK32
# cat<<EOF
# [STAGE:RestoreTitle]
# STAGECLASS gencodes.RestoreTitlesStage
# INPUTS POSTEPIK32_OUT,
# OUTPUTS LIGPREP_OUT,
# EOF
Ligand_name="LIGPREP_OUT"
TO_RMSD="${Ligand_name}"
}
RS1(){
cat<<RS1 >> ${Inp_Name}
[STAGE:PRE_RS1]
STAGECLASS gencodes.RecombineStage
INPUTS ${Ligand_name},
OUTPUTS PRE_RS1_RECOMBINE_OUT,
NUMOUT njobs
OUTFORMAT maegz
MIN_SUBJOB_STS 4000
MAX_SUBJOB_STS 40000
GENCODES YES
OUTCOMPOUNDFIELD s_vsw_compound_code
OUTVARIANTFIELD s_vsw_variant
UNIQUEFIELD s_m_title
[STAGE:RS1]
STAGECLASS macromodel.SampleRingsStage
INPUTS PRE_RS1_RECOMBINE_OUT,
OUTPUTS RS1_OUT,
RECOMBINE YES
FORCE_FIELD ${Force_Field}
SOLVENT Water
ELECTROSTATIC_TREATMENT Constant dielectric
CHARGES_FROM Force field
MAXIMUM_ITERATION 300
OUTCONFS_PER_SEARCH 2
[USEROUTS:${task}]
USEROUTS RS1_OUT,
STRUCTOUT RS1_OUT
RS1
Ligand_name="RS1_OUT"
TO_RMSD="${Ligand_name}"
}
RS4(){
cat<<RS4 >> ${Inp_Name}
[STAGE:PRE_RS4]
STAGECLASS gencodes.RecombineStage
INPUTS ${Ligand_name},
OUTPUTS PRE_RS4_RECOMBINE_OUT,
NUMOUT njobs
OUTFORMAT maegz
MIN_SUBJOB_STS 4000
MAX_SUBJOB_STS 40000
GENCODES YES
OUTCOMPOUNDFIELD s_vsw_compound_code
OUTVARIANTFIELD s_vsw_variant
UNIQUEFIELD s_m_title
[STAGE:RS4]
STAGECLASS macromodel.SampleRingsStage
INPUTS PRE_RS4_RECOMBINE_OUT,
OUTPUTS RS4_OUT,
RECOMBINE YES
FORCE_FIELD ${Force_Field}
SOLVENT Water
ELECTROSTATIC_TREATMENT Constant dielectric
CHARGES_FROM Force field
MAXIMUM_ITERATION 500
OUTCONFS_PER_SEARCH 8
[USEROUTS:${task}]
USEROUTS RS4_OUT,
STRUCTOUT RS4_OUT
RS4
Ligand_name="RS4_OUT"
TO_RMSD="${Ligand_name}"
}
RS_Fast(){
cat<<RS_Fast >> ${Inp_Name}
[STAGE:PRE_RS_Fast]
STAGECLASS gencodes.RecombineStage
INPUTS ${Ligand_name},
OUTPUTS PRE_RS_Fast_RECOMBINE_OUT,
NUMOUT njobs
OUTFORMAT maegz
MIN_SUBJOB_STS 4000
MAX_SUBJOB_STS 40000
GENCODES YES
OUTCOMPOUNDFIELD s_vsw_compound_code
OUTVARIANTFIELD s_vsw_variant
UNIQUEFIELD s_m_title
[STAGE:RS_Fast]
STAGECLASS macromodel.SampleRingsStage
INPUTS PRE_RS_Fast_RECOMBINE_OUT,
OUTPUTS RS_Fast_OUT,
RECOMBINE YES
FORCE_FIELD ${Force_Field}
SOLVENT Water
ELECTROSTATIC_TREATMENT Constant dielectric
CHARGES_FROM Force field
MAXIMUM_ITERATION 100
OUTCONFS_PER_SEARCH 2