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MAIN
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MAIN
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#!/usr/bin/perl
$current_time = localtime;
srand(time ^ $$ ^ unpack "%L*", 'ps axww | gzip');
$leaexe=$0;
#windows requires 2 steps
$leaexe=~s/MAIN$//;
$leaexe=~s/\/$//;
#print "perl scripts in $leaexe\n";
$platform=$^O;
print "perl scripts in $leaexe on platform $platform\n";
# platform = linux MSWin32
$inputfile='';
$visubase='';
$visufgt='';
$evalfile='';
$substfile='';
$inputfileold='';
local($inputfile,$visubase,$visufgt)=@ARGV;
if ($inputfile eq ''){
die "\n
HELP/INFORMATION : lea -i \n\n";
};
$leafgt=$leaexe."/LEGO";
$convertor=$leaexe."/rdkit-confs.py";
$inputfileold=$inputfile;
$optionlea=""; # empty then launch genetic algorithm by lea else launch option -e, -v, or -r
if($inputfile eq "-v"){
$optionlea="-v";
$inputfile=$visubase;
$molecule=$visufgt;
die "no fragments ??\n" if(! -e $visufgt || -z $visufgt);
}
elsif($inputfile eq "-e"){
$optionlea="-e";
$inputfile=$visubase;
$evalfile=$visufgt;
die "FILE $evalfile not found or empty ??\n" if((! -e $evalfile) || (-z $evalfile));
}
elsif($inputfile eq "-r"){
$optionlea="-r";
$inputfile=$visubase;
};
################################################
if($inputfile eq "-i"){
$text="
########################################################################
LEA3D v3.0
########################################################################
Ligand by Evolutionary Algorithm
Author: D. Douguet
########################################################################
References:
Douguet D., Munier-Lehmann H., Labesse G. and
Pochet S., LEA3D: A Computer-Aided Ligand Design for
Structure-Based Drug Design, J. Med. Chem., 2005, 48, 2457-2468.
doi: 10.1021/jm0492296
Douguet D., Thoreau E. and Grassy G., LEA (Ligand by Evolutionary
Algorithm): A Genetic Algorithm for the Automated Generation of
Small Organic Molecules, J. Comput.-Aided Mol. Design, 2000, 14, 449-466.
doi: 10.1023/A:1008108423895
########################################################################
General Command list:
lea -i
lea -e <ligand.in> <file.sdf>
lea -r <ligand.in>
lea <ligand.in>
lea -v <ligand.in> <file with one molecule per line (e.g.: 1*5-3*1_1*6-2*1 / 16 1220 1361 )>
########################################################################
\n";
print "$text";
die "\n";
};
######################################################## SUBROUTINES
#BOS.pl gather Build Optimis and Score
require "$leaexe/BOS.pl";
require "$leaexe/BUILD.pl";
require "$leaexe/OPTIMIS.pl";
require "$leaexe/FILTER.pl";
require "$leaexe/SCORE.pl";
require "$leaexe/SCALE.pl";
require "$leaexe/CHILD.pl";
require "$leaexe/CHEMICAL_FUNCTIONS.pl";
#require "$leaexe/PHARMACOPHORE.pl";
require "$leaexe/AUTO_ADAPT.pl";
#require "$leaexe/DOCKING.pl";
# CLEAN directory
unlink "fitmoy.dat" if(-e "fitmoy.dat");
unlink "scaffold.sdf" if(-e "scaffold.sdf");
unlink "summary.out" if(-e "summary.out");
unlink "operators.out" if(-e "operators.out");
unlink "edesign.sdf" if(-e "edesign.sdf");
############################### INITIALISATION DES PARAMETRES et de la POOL Lit $inputfile
print "\n";
print ('/'x80);
print "\n";
print "\n\t\t LEA3D V3.0\n";
print "\n";
print ('/'x80);
print "\n";
%param=(
'UNIX',0,
'LINUX',1,
'WORKDIR',0,
'VERBOSITY',0,
'GENMAX',50,
'POP',40,
'SCALEMAX',6,
'SCALEMIN',2,
'PROBA_CROSS',30,
'PROBA_MUT',70,
'ELITISM',0,
'LONGGEN',0,
'GET_POOL',0,
'FILTER',0,
'SCAFFOLD',0,
'OPTIMIS',0,
'NBCONF',0,
'FUNCTION',0,
'CHARGES',0,
'SCORE100',0,
'START',0,
'LEGODB',1,
);
$param{WORKDIR}=".";
print "WORKING DIRECTORY : $param{WORKDIR}\n" if($param{VERBOSITY} > 0);
############################### LECTURE DES PARAMETRES DE AG
@bn='';
$ibn=0;
$flag=1;
$scaffoldpoints="";
$paramdrug=" P 3D - - T - I ";
open(PARAM,"<$inputfile");
while (<PARAM>){
@get = split(' ',$_);
if ($flag == 0 && $_!~/^#/ && $get[0] ne ''){
$bn[$ibn]=$get[0];
$ibn++;
};
if($_=~/^BASES/){
$flag=0;
};
if($_=~/^SCAFFOLD/){
@get2=@get;
$get2[0]="";
$get2[1]="";
$scaffoldpoints=join(' ',@get2) if($get[2] ne "");
};
if($_=~/^FILTER/){
if($get[1] ne "0"){
$len=@get;
if($len==9){
$paramdrug="$get[1] $get[2] $get[3] $get[4] $get[5] $get[6] $get[7]";
}
else{
print "Unexpected number of parameters for the keyword FILTER (defaults are set: $paramdrug) !!\n";
};
};
};
if ($_!~/^#/ && $flag && $get[0] ne ''){
$param{$get[0]}=$get[1];
$param{FILTER}=1 if($get[0] eq "FILTER" && $get[1] ne "0");
$param{SCAFFOLD}='0' if($param{SCAFFOLD} eq '' && $get[0] eq "SCAFFOLD");
$param{GET_POOL}='0' if($param{GET_POOL} eq '' && $get[0] eq "GET_POOL");
$param{START}='0' if($param{START} eq '' && $get[0] eq "START");
die "GET_POOL $param{GET_POOL} not found or empty ??\n" if($get[0] eq "GET_POOL" && $param{GET_POOL} ne '0' && ((! -e "$param{GET_POOL}") || (-z "$param{GET_POOL}")));
die "SCAFFOLD $param{SCAFFOLD} not found or empty ??\n" if($get[0] eq "SCAFFOLD" && $param{SCAFFOLD} ne '0' && ((! -e "$param{SCAFFOLD}") || (-z "$param{SCAFFOLD}")));
if($param{START} ne '0' && ((! -e "$param{START}") || (-z "$param{START}"))){
if( (-e "$leaexe/LEGO/$param{START}") && (! -z "$leaexe/LEGO/$param{START}")){
$param{START}=$leaexe."/LEGO/".$param{START};
}
else{
die "START $param{START} not found or empty ??\n";
};
};
if($_=~/^CHARGES/){
if($get[1] == 1 && ($get[2] eq 'GAS' || $get[2] eq 'AM1')){
$param{CHARGES}=$get[2];
}
else{
$param{CHARGES}='0';
};
};
#print "$get[0]\t$param{$get[0]} $get[2] $get[3]\n";
};
};
close(PARAM);
print "\n";
$param{LONGGEN} = 10 if($param{LONGGEN} > 10);
die "Parameter ELITISM and POP are not compatible with a genetic algorithm\n" if($param{POP} <= $param{ELITISM});
die "Parameter POP must be > 0\n" if($param{POP} <= 0);
##################################################################################
if(($optionlea eq "-e" || $optionlea eq "") && ($param{FUNCTION} eq '' || $param{FUNCTION} eq '0')){
die "FUNCTION file not found ????\n";
};
################################ Program d'EVALUATION
# option -e
if($optionlea eq "-e"){
#read the $evalfile, save datablock and sdf into global memory
$memoi=-1;
$flagnew=1;
open(PARAM,"<$evalfile");
while (<PARAM>){
if ($flagnew){
$flagnew=0;
$memoi++;
# global memory
$memo_gi[$memoi]=$memoi;
$memo_gen[$memoi]=0;
$memo_mol[$memoi]=1;
$memo_molping[$memoi]=$memoi;
$memo_datablock[$memoi]="";
$memo_remark[$memoi]="";
$memo_conf[$memoi]=1;
$memo_nbconf[$memoi]=1;
$memo_score[$memoi]=0;
$memo_properties[$memoi]="";
$memo_rank[$memoi]=0;
$memo_sdf[$memoi]="";
$memo_mol2[$memoi]="";
};
$conv2=$_;
$flagpoint=1 if($conv2 =~/^>/);
if($conv2 =~/\$\$\$\$/){
$flagnew=1;
$flagpoint=0;
};
if($flagpoint){
$memo_datablock[$memoi]=$memo_datablock[$memoi].$_;
}
else{
$memo_sdf[$memoi]=$memo_sdf[$memoi].$_; #original sdf ie $memo_conf[$memoi]==0
};
};
close(PARAM);
$nbevalfile=@memo_gi;
#&memo_print(0,1,$nbevalfile,"");
};
################################ PRINT DES PARAMETRES DE LEA
if($optionlea eq "" || $optionlea eq "-e" || $optionlea eq "-r"){
print "\n";
print "PARAMETERS : \n\n";
if($optionlea eq ""){
print "Genetic algorithm: $param{GENMAX} generations of $param{POP} molecules (composition with LONGGEN=$param{LONGGEN})\n";
print "Genetic algorithm: Mutation probability=$param{PROBA_MUT} and Crossover probability=$param{PROBA_CROSS}\n";
#print "Genetic algorithm: Selection pressure [$param{SCALEMIN} - $param{SCALEMAX}] and elitism=$param{ELITISM}\n";
print "Genetic algorithm: elitism=$param{ELITISM}\n";
print "Genetic algorithm: obligate fragment $param{SCAFFOLD}\n" if($param{SCAFFOLD} != 0);
print "Use the initial population $param{START}\n" if($param{START} ne '0');
print "\n";
};
print "Function from $param{FUNCTION}\n";
print "Use $param{GET_POOL} to react with SCAFFOLD\n" if($param{GET_POOL} != 0);
$convertor2=$convertor;
$convertor2=~s/(.*)\/(.*)/$2/;
print "Use 3D generator program $convertor2\n" if($param{OPTIMIS}==1);
print "Conformers: up to $param{NBCONF}\n" if($param{OPTIMIS}==1);
print "No optimization\n" if($param{OPTIMIS}==0);
print "Charge calculation $param{CHARGES}\n" if($param{CHARGES} != 0);
print "Filtering and ionization step: $paramdrug\n" if($param{FILTER}==1);
print "No FILTER\n" if($param{FILTER}==0);
print "Discard molecule if score < $param{SCORE100} %\n" if($param{SCORE100}>0);
print "Verbosity=$param{VERBOSITY}\n";
if($param{VERBOSITY} >= 1){
@clefs= keys %param;
@valeurs= values %param;
foreach $i (0..@clefs){
print "$clefs[$i] \t $valeurs[$i]\n";
};
};
};
################################ Program click reactants on a scaffold
# option -r
if($param{SCAFFOLD} ne '0' && $param{GET_POOL} ne '0' && $optionlea eq "-r"){
if(!-e "$param{GET_POOL}" || -z "$param{GET_POOL}"){
die "Error in option -r: $param{GET_POOL} not found !\n";
}
else{
#Check for X dummy atoms
$rep="";
#chop($rep=`grep 'X' $param{GET_POOL} | wc -l`);
open(PARAM,"<$param{GET_POOL}");
while(<PARAM>){
if($_=~/ X /){
$rep=1;
};
};
close(PARAM);
#$rep=~s/ //g;
if($rep eq "" || $rep==0){
die "Error in option -r: $param{GET_POOL} does not contain X anchors\n";
}
else{
#chop($rep=`$leaexe/GET_X.pl $param{GET_POOL}`);
#rename "new_$param{GET_POOL}", $param{GET_POOL};
&getx($param{GET_POOL},"getx.sdf");
rename "getx.sdf", $param{GET_POOL};
};
$param{LONGGEN}=2;
$param{GENMAX}=0;
#chop($nbconformer = `$leaexe/NBSDF.pl $param{GET_POOL}`);
$nbconformer=&nbsdf($param{GET_POOL});
$param{POP}=$nbconformer;
};
}
elsif($optionlea eq "-r"){
die "Error in option -r: you need to set GET_POOL and SCAFFOLD\n";
};
################################ CHECK LEGO LIBRARIES
if($optionlea eq "" || $optionlea eq "-v" || $optionlea eq "-r"){
if($optionlea eq "" || $optionlea eq "-v"){
print "\nBASES : \n";
if($bn[0] eq ""){
print "no fragment database have been selected. Get LEGO from eDESIGN:\n";
if($platform eq "linux" || $platform eq "darwin"){
#chop($tmp=`ls $leafgt/*.sdf`);
#print "$tmp\n";
$tmp="$leafgt/all.sdf";
}
else{
$tmp="$leafgt/all.sdf";
};
@getbase=split(' ',$tmp);
$ibn=0;
foreach $i (0..@getbase-1){
if(-e $getbase[$i]){
$bn[$ibn]=$getbase[$i];
$ibn++;
};
};
};
}
elsif($optionlea eq "-r"){
@bn="";
$ibn=0;
$bn[$ibn]=$param{GET_POOL};
$ibn++;
print "\nGET POOL:\n";
};
#Add frequencies information (frequencies.txt) if read $leafgt/all.sdf
@legofreq=""; # used if frequencies exist (eg: frequencies.txt for all.sdf)
$sumfreq=0;
if($ibn==1 && $bn[0]=~/all\.sdf/ && -e "$leafgt/frequencies.txt"){
$fi=1;
open(PARAM,"<$leafgt/frequencies.txt");
while(<PARAM>){
@get = split('\n',$_);
$legofreq[$fi]=$get[0];
$sumfreq=$sumfreq+$get[0];
$fi++;
};
close(PARAM);
$fi=$fi-1;
};
@lego="";
@legono="";
@typelego="";#nb of X
@points="";
@legodatablock="";
#read lego datablocks <GC>
@legogc="";
#read lego datablocks <ncycles> <natomescycle> <cyclearom> <nhetat> <ARcenter> <LIPcenter> <nbringar> <natomes> <nrotatable>
@legoc="";#number of rings
@legonba="";#number of atoms
@legolip="";#lip center of mass (if not then it exists an ar center of mass (exclusive))
$legoi=1; # position 0 is allocated to the submitted scaffold if any
$bnmol=0;
$singlea=0;
$multiplea=0;
foreach $i (0..@bn-1){
if((!-e "$param{WORKDIR}/$bn[$i]") && (!-e "$leaexe/LEGO/$bn[$i]") && (!-e "$bn[$i]")){
die "Library $bn[$i] not found ! \n";
}
elsif(-e "$param{WORKDIR}/$bn[$i]"){
open(PARAM,"<$bn[$i]");
$legointernes="";
}
elsif(-e "$bn[$i]"){
open(PARAM,"<$bn[$i]");
$legointernes="";
}
else{
open(PARAM,"<$leaexe/LEGO/$bn[$i]");
$legointernes="$leaexe/LEGO/";
};
$flagnew=1;
$legonoi=0;
while(<PARAM>){
if ($flagnew){
$bnmol++;
$flagnew=0;
$flagpoint=0;
$flagpointdatablock=0;
$register=0;
$flaggc=0;#if GC (Ghose and Crippen atom types)
$flagc=0;#number of rings
$flagnba=0;#number of atoms
$flaglip=0;#x coordinate of lip center of mass (acyclic only)
$legonoi++;
};
$conv2=$_;
if($flaggc && ($conv2!~/^>/ && $conv2 ne "")){
@get = split('\n',$_);
$legogc[$legoi]=$get[0];
$flaggc=0;
};
if($flagc && ($conv2!~/^>/ && $conv2 ne "")){
@get = split('\n',$_);
$legoc[$legoi]=$get[0];
$flagc=0;
};
if($flagnba && ($conv2!~/^>/ && $conv2 ne "")){
@get = split('\n',$_);
$legonba[$legoi]=$get[0];
$flagnba=0;
};
if($flaglip && ($conv2!~/^>/ && $conv2 ne "")){
@get = split('\n',$_);
$legolip[$legoi]=$get[0];
$flaglip=0;
};
if($flagpoint && ($conv2!~/^>/ && $conv2 ne "")){
@get = split(' ',$_);
@getpoint=split('-',$get[0]);
$nbpoints=@getpoint;
if($nbpoints > 0){
$points[$legoi]=join(" ",@getpoint);
$points[$legoi]=" ".$points[$legoi]." ";
$typelego[$legoi]=$nbpoints;
$lego[$legoi]=$legointernes.$bn[$i];
$legono[$legoi]=$legonoi;
$singlea++ if($nbpoints == 1);
$multiplea++ if($nbpoints > 1);
print "Register $legoi library file sdf $lego[$legoi] no $legono[$legoi] number of anchors = $typelego[$legoi] points -$points[$legoi]-\n" if($param{VERBOSITY} > 0);
#$legoi++;
$register=1;
$flagpoint=0;
};
};
$flagpoint=1 if($conv2 =~/POINTS/ && $conv2 =~/^>/);
$flagpointdatablock=1 if($conv2 =~/^>/);
$flagpointdatablock=0 if($conv2 =~/POINTS/);
$flaggc=1 if($conv2 =~/<GC>/ && $conv2 =~/^>/);
$flagc=1 if($conv2 =~/<ncycles>/ && $conv2 =~/^>/);
$flagnba=1 if($conv2 =~/<natomescycle>/ && $conv2 =~/^>/);
$flagnba=1 if($conv2 =~/<natomes>/ && $conv2 =~/^>/);
$flaglip=1 if($conv2 =~/<LIPcenter>/ && $conv2 =~/^>/);
if($conv2 =~/\$\$\$\$/){
$flagpointdatablock=0;
#print "Warning: legogc $legoi null\n" if($legogc[$legoi]!~/\d/);
$legoi++;
$flagnew=1;
if($register==0){
print "Registering molecule no $bnmol from $legointernes $bn[$i] failed\n" if($param{VERBOSITY} > 0);
};
};
if($flagpointdatablock && $optionlea eq "-r"){
$legodatablock[$legoi]=$legodatablock[$legoi].$_;
};
};
close(PARAM);
};
$legoi=$legoi-1;
if($legoi == 0){
die "No Fragments !! Please select at least one fragment database (sdf file with datablock <POINTS>) under the keyword BASES in the input file .inp\n";
}
else{
if($fi==$bnmol){
print "$bnmol molecules read with associated frequencies (frequencies.txt, sum=$sumfreq), $legoi fragments (single anchor = $singlea ; multiple anchors = $multiplea)\n";
}
else{
$sumfreq=0;
print "$bnmol molecules read, $legoi fragments (single anchor = $singlea ; multiple anchors = $multiplea)\n";
};
};
};
################################# SCAFFOLD: case of one obligate fragment
# option SCAFFOLD
if(($optionlea eq "" || $optionlea eq "-r" || $optionlea eq "-v") && $param{SCAFFOLD} ne '0'){
print "\nSCAFFOLD:\n";
if($scaffoldpoints eq ""){
#perhaps <POINTS>
$rep="";
#chop($rep=`grep 'POINTS' $param{SCAFFOLD} | wc -l`);
open(PARAM,"<$param{SCAFFOLD}");
while(<PARAM>){
if($_=~/<POINTS>/){
$rep=1;
};
};
close(PARAM);
#$rep=~s/ //g;
if($rep eq "" || $rep==0){
#perhaps X dummy atoms ?
#chop($rep=`$leaexe/GET_X.pl $param{SCAFFOLD}`);
#rename "new_$param{SCAFFOLD}", $param{SCAFFOLD};
&getx($param{SCAFFOLD},"getx.sdf");
rename "getx.sdf", $param{SCAFFOLD};
print "Search for 'X' and update POINTS $param{SCAFFOLD}\n";
};
};
$nbscaffold=0;
$print=0;
$flagpoints=0;
open(IN2,"<$param{SCAFFOLD}");
open(INS,">scaffold.sdf");
# if -r:
# accept several scaffold with same numbering scheme e.g. product of round 0 with same scaffold for all products (lea writes scaffold first in the sdf so the numbering scheme is maintained)
$scaffoldpointso=$scaffoldpoints;
while(<IN2>){
$print=1 if($_ =~/^>/);
if ($_=~/\$\$\$\$/){
$nbscaffold++;
if($scaffoldpoints ne ""){
@pointsscaff=split(' ',$scaffoldpoints);
$tmppoints=join('-',@pointsscaff);
print "write $tmppoints into scaffold.sdf (compound no $nbscaffold)\n" if($param{VERBOSITY} > 0);
print INS "> <POINTS>\n";
print INS "$tmppoints\n\n";
print INS "\$\$\$\$\n";
$nbpoints=@pointsscaff;
print "scaffold.sdf with $nbpoints anchors\n";
if($optionlea eq "-r" && $nbpoints > 1){
die "Error in option -r: more than one anchor points (=$nbpoints) (X dummy atom) in SCAFFOLD (compound no $nbscaffold). That may produce the wrong product\n";
};
if($nbscaffold==1){
$lego[0]="scaffold.sdf";
$points[0]=$scaffoldpoints;
$typelego[0]=$nbpoints;
$legono[0]=1;
$singlea++ if($nbpoints == 1);
$multiplea++ if($nbpoints > 1);
print "SCAFFOLD Register 0 library file sdf $lego[0] no $legono[0] number of anchors = $typelego[0] points -$points[0]-\n" if($param{VERBOSITY} > 0);
}
else{
# do not update $legoi (refered to the number of lego in @lego)
# $legoi++
$indicelego=@lego;
$lego[$indicelego]="scaffold.sdf";
$points[$indicelego]=$scaffoldpoints;
$typelego[$indicelego]=$nbpoints;
$legono[$indicelego]=$nbscaffold;
# do not update $singlea neither $multiplea
#$singlea++ if($nbpoints == 1);
#$multiplea++ if($nbpoints > 1);
print "SCAFFOLD Register $indicelego library file sdf $lego[$indicelego] no $legono[$indicelego] number of anchors = $typelego[$indicelego] points -$points[$indicelego]-\n" if($param{VERBOSITY} > 0);
};
}
elsif($scaffoldpoints eq ""){
die "no POINTS neither in $param{SCAFFOLD} (compound no $nbscaffold) nor in parameter SCAFFOLD\n";
}
elsif($nbscaffold == 2 && $optionlea eq "-r"){
print "Warning: several scaffolds in $param{SCAFFOLD}: each of them will be combined !\n";
}
elsif($nbscaffold == 2){
print "Warning: several scaffolds in $param{SCAFFOLD}: only the first one selected !\n";
};
if($optionlea eq "-r"){
$print=0;
$scaffoldpoints="" if($scaffoldpointso eq "");
}
else{
$print=1;
};
}
elsif($print==0){
print INS "$_";
};
if($flagpoints && $scaffoldpoints eq ""){
@get=split(' ',$_);
@getpoint=split('-',$get[0]);
$scaffoldpoints=join(' ',@getpoint);
$flagpoints=0;
};
$flagpoints=1 if($_ =~/^>/ && $_ =~/POINTS/);
};
close(IN2);
close(INS);
};
################################# Program to build one molecule from fragment numbers
# option -v
if($optionlea eq "-v"){
$gi=0;
open(INS,"<$molecule");
while(<INS>){
$_=~s/\n$//;
@get=split('\/',$_);
$get[0]=~s/ //g;
$mol[$gi]=$get[0];
$molping[$gi]=$get[1];
#print "$mol[$gi]\n";
#print "$molping[$gi]\n";
$gi++;
};
close(INS);
print "\n";
foreach $gi (0..@mol-1){
$moleculei=$gi;
$nomtab="parent";
&build;
$gi2=$gi+1;
if(-e "mol.sdf" && !-z "mol.sdf"){
rename "mol.sdf", "mol_$gi2.sdf";
print "$molecule($gi2) $mol[$gi] / $molping[$gi] : see mol_$gi2.sdf\n";
}
else{
print "Building $molecule($gi2) failed\n";
};
};
die "Molecules are in mol_*.sdf\n";
};
###################################### Check compatibility with LONGGEN
if($optionlea eq ""){
if($param{SCAFFOLD} eq '0'){
if($multiplea == 0 && $param{LONGGEN} > 2 ){
die ("No multi-substituents fragments and LONGGEN > 2 are incompatibles parameters !\n");
};
if($multiplea == 0 && $param{LONGGEN} ==0){
print "Warning LONGGEN set to 2 because No multi-substituents fragments and LONGGEN > 2 are incompatibles parameters !\n";
$param{LONGGEN}=2;
};
}
else{ # $param{SCAFFOLD} set with one or more anchors !
@pointsscaff=split(' ',$scaffoldpoints);
$tmppoints=join('-',@pointsscaff);
if($multiplea ==1 && $tmppoints > 1 && $tmppoints < ($param{LONGGEN}-1) && $param{LONGGEN} > 0){ #$multiplea==scaffold
die ("only scaffold as multi-substituents fragment and LONGGEN is too high compared to the number of anchors\n");
}
elsif($param{LONGGEN} ==0 && $multiplea ==1 && $tmppoints==1){
$param{LONGGEN}=2;
print "Warning LONGGEN set to 2 because only scaffold as multi-substituents fragment with $tmppoints anchor\n";
}
elsif($param{LONGGEN} ==0 && $multiplea ==1){
$param{LONGGEN}=$tmppoints+1;
$param{LONGGEN}=10 if($param{LONGGEN} > 10);
print "Warning LONGGEN set to $param{LONGGEN} because only scaffold as multi-substituents fragment with $tmppoints anchors\n";
};
};
};
###################################### READ FUNCTION parameters
%prop=(
'dock',0.0,
'gnp',0.0,
'psa',0.0,
'volume',0.0,
'area',0.0,
'mm',0.0,
'logp',0.0,
'mr',0.0,
'rg',0.0,
'ix',0.0,
'iy',0.0,
'iz',0.0,
'length',0.0,
'nbhd',0.0,
'nbha',0.0,
'nbatom',0.0,
'dipole',0.0,
'solubility',0.0,
'function',0.0,
'lipinski',0.0,
'pharm',0.0,
'rot',0.0,
'nring',0.0,
'nringa',0.0,
'fingerprint',0.0,
'shape',0.0,
'exactmatch',0.0,
);
die "FILE $param{FUNCTION} do not exists\n" if(! -e $param{FUNCTION} && ($optionlea eq "-e" || $optionlea eq ""));
@fprop='';
@fmin='';
@fmax='';
@fw='';
$i=0;
$flagdock_apolar_sas=0;
$rmsdock=5; # distance site actif > 5 A alors score de 0
$docki=0;
$docking_program="FLEXX"; #default
@protfmin='';
@protfmax='';
@protfw='';
@prot='';
@site='';
@refx='';
@refy='';
@refz='';
@rmsdock='';
@limitscore='';
@file_bat='';
@specificity='';
@interaction='';
@interactionif='';
@mininteraction='';
@maxinteraction='';
$interaci=0;
# used by $leaexe/interactpdbmol2 to print interactions up to $distmaxinteract
$distmaxinteract=20.0;
# charges bumping
$distchargebumping="";
$fingerref="";
$evaluate_prop=0;
$evaluate_finger=0;
$evaluate_dock=0;
$evaluate_pharm=0;
$evaluate_function=0;
$evaluate_shape=0;
$evaluate_exactmatch=0;
#default
#$evaluate_prop=1;
$textpharm="";
open(PARAM,"<$param{FUNCTION}");
while (<PARAM>){
@get = split(' ',$_);
if($get[0] ne '' && $get[0]!~/^#/ && $get[0] ne "interaction" && $get[3] > 0){
$get[0]='mm' if($get[0] eq 'mw');
$fprop[$i]=$get[0];
$fmin[$i]=$get[1];
$fmin[$i]="" if($fmin[$i] eq "-");
$fmax[$i]=$get[2];
$fmax[$i]="" if($fmax[$i] eq "-");
$fw[$i]=$get[3];
$evaluate_prop=1 if($get[0] eq "psa" || $get[0] eq "volume" || $get[0] eq "area" || $get[0] eq "mm" || $get[0] eq "logp" || $get[0] eq "fsp3" || $get[0] eq "complexity" || $get[0] eq "mr" || $get[0] eq "rg" || $get[0] eq "ix" || $get[0] eq "iy" || $get[0] eq "iz" || $get[0] eq "length" || $get[0] eq "nbhd" || $get[0] eq "nbha" || $get[0] eq "nbatom" || $get[0] eq "dipole" || $get[0] eq "solubility" || $get[0] eq "lipinski" || $get[0] eq "rot" || $get[0] eq "nringa" || $get[0] eq "nring");
if($get[0] eq 'fingerprint'){
$simdescriptor=$get[4];
$fingerref=$get[6];
$simmeasure=$get[5];
$evaluate_finger=1;
};
if($get[0] eq 'shape'){
$shaperef=$get[4];
$shapescore=$get[5];
$evaluate_shape=1;
};
if($get[0] eq 'exactmatch'){
$evaluate_exactmatch=1;
$exactmatchref=$get[4];
};
if($get[0] eq 'function'){
$fprop[$i]="function";
$listefonction=$get[4];
$fmin[$i]=1;
$fmax[$i]=1;
$evaluate_function=1;
};
if($get[0] eq 'lipinski'){
$fmin[$i]=1;
$fmax[$i]=1;
};
if($get[0] eq 'pharmacophore'){
$evaluate_pharm=1;
$fprop[$i]="pharm";
$fmin[$i]=1;
$fmax[$i]=1;
$get[0]="";
$get[1]="";
$get[2]="";
$get[3]="";
$listepharm=join(' ',@get);
$textpharm="Pharmacophore:\n";
@getvacpharm1='';
@getvacpharm2='';
@getvacmin='';
@getvacmax='';
@getvac=split(' ',$listepharm);
$pharmj=3;
$pharmk=0;
foreach $pharmi (0..@getvac-1){
if($pharmi == ($pharmj-3) && $getvac[$pharmi] ne "" && $getvac[$pharmi+1] ne "" && $getvac[$pharmi+2] ne "" && $getvac[$pharmi+3] ne ""){
$getvacpharm1[$pharmk]=$getvac[$pharmi];
$getvacpharm2[$pharmk]=$getvac[$pharmi+1];
$getvacmin[$pharmk]=$getvac[$pharmi+2];
$getvacmax[$pharmk]=$getvac[$pharmi+3];
$pharmj=$pharmj+4;
$pharmk++;
$textpharm=$textpharm."Pairwise $pharmk: $getvac[$pharmi] $getvac[$pharmi+1] with [$getvac[$pharmi+2] <= d <= $getvac[$pharmi+3]]\n";
};
};
print "\n";
};
if($fprop[$i] eq 'gnp' && $fw[$i] != 0){
$flagdock_apolar_sas=1; # flag necessaire pour plus tard !
};
if($fprop[$i] =~/dock/ && $fw[$i] != 0 && $fprop[$i] ne 'gnp'){
$evaluate_dock=1;
if($get[4] eq '' || $get[5] eq '' || $get[6] eq '' || $get[7] eq '' || $get[8] eq '' || $get[9] eq '' || $get[10] eq ''){
die "Il manque des parametres pour la fonction docking $get[0] : \ndock -60 0 0.0 protein.pdb site.pdb refx refy refz tolerance_radius minimum_flexx_score file.bat(or '-')\n";
};
if($docki > 0 && $get[12] eq ''){
die "No defined specificity for $get[4]: must be set relative to the first dock $prot[0] (ie AND, OR, NOT) ! \n";
};
$protfmin[$docki]=$get[1];
$protfmax[$docki]=$get[2];
$protfw[$docki]=$get[3];
$prot[$docki]=$get[4];
$site[$docki]=$get[5];
$refx[$docki]=$get[6];
$refy[$docki]=$get[7];
$refz[$docki]=$get[8];
$rmsdock[$docki]=$get[9];
$limitscore[$docki]=$get[10];
$file_bat[$docki]=$get[11];
$file_bat[$docki]='' if($file_bat[$docki] eq '-');
$specificity[$docki]=$get[12] if($docki > 0);
$specificity[$docki]=~tr/[a-z]/[A-Z]/;
@getnp=split('\.',$prot[$docki]);
$protdir[$docki]=$getnp[0];
if(-e "$protdir[$docki]"){
system("rm -rf $protdir[$docki]");
system("mkdir $protdir[$docki]");
}
else{
system("mkdir $protdir[$docki]");
};
if($docki>0){
$fprop[$i]="";
$fmin[$i]="";
$fmax[$i]="";
$fw[$i]="";
$i=$i-1;#$fprop must have only one dock
};
$docki++;
};
$i++;
}
elsif($get[0] eq "interaction" && $_=~/ PROT_/ && $_=~/ LIG_/){
$interactionif[$interaci]=1 if($_=~/ IF / || $_=~/ if /);
$maxinteraction[$interaci]=3.1 if($_!~/DIST_MAX_/);
$mininteraction[$interaci]=0.0 if($_!~/DIST_MIN_/);
foreach $ini (1..@get-1){
if($get[$ini]=~/DIST_MAX_/){
$maxinteraction[$interaci]=$get[$ini];
$maxinteraction[$interaci]=~s/DIST_MAX_//g;
$distmaxinteract=$maxinteraction[$interaci] if($maxinteraction[$interaci] > $distmaxinteract);
}
elsif($get[$ini]=~/DIST_MIN_/){
$mininteraction[$interaci]=$get[$ini];
$mininteraction[$interaci]=~s/DIST_MIN_//g;
}
else{
$interaction[$interaci]=$interaction[$interaci]." $get[$ini] " if($get[$ini] ne "IF" && $get[$ini] ne 'if');
};
};
$interaci++;
}