int main(int argc, char** argv)
{
Path path;
String tmp;
String configuration_string = "";
CommandlineParser parpars("SLICK", "scoring protein-carbohydrate interactions", VERSION, String(__DATE__), "Scoring");
parpars.registerFlag("E", "compute only SLICKEnergy");
parpars.registerFlag("S", "compute only SLICKScore");
parpars.registerFlag("u", "unite atoms");
parpars.registerFlag("n", "read radius rules for the nonpolar solvation from FILE");
parpars.registerFlag("N", "scale nonpolar radii by FACTOR");
parpars.registerFlag("log", "write log file");
parpars.registerMandatoryInputFile("rec", "input receptor file");
parpars.registerMandatoryInputFile("lig", "input ligand file");
parpars.registerOptionalInputFile("cr", "charge rules");
parpars.registerOptionalInputFile("pr", "radius rules for the polar solvation");
parpars.registerOptionalInputFile("lj", "use FILE for LJ parameters");
parpars.registerOptionalInputFile("op", "read options from FILE (command line overrides!)");
parpars.registerOptionalIntegerParameter("v", "verbosity to level");
parpars.registerOptionalDoubleParameter("s", "scaling factor for receptor charges");
parpars.registerOptionalDoubleParameter("t", "scaling factor for ligand charges");
parpars.setSupportedFormats("rec","PDB");
parpars.setSupportedFormats("lig","HIN");
parpars.setSupportedFormats("cr","rul");
parpars.setSupportedFormats("pr","rul");
parpars.setSupportedFormats("lj","rul");
parpars.setSupportedFormats("op", "ini");
String man = "This tool calculates the SLICKEnergy / SLICK Score for protein-carbohydrate complexes.";
parpars.setToolManual(man);
parpars.parse(argc, argv);
Options options;
ScoringFunction::getDefaultOptions(options);
unsigned int verbosity = 0;
if (parpars.get("v") != CommandlineParser::NOT_FOUND)
{
verbosity = parpars.get("v").toInt();
options.setInteger("verbosity", verbosity);
}
float receptor_charge_scaling_factor = 1.0f;
if (parpars.get("s") != CommandlineParser::NOT_FOUND)
{
receptor_charge_scaling_factor = parpars.get("s").toFloat();
configuration_string += "scale_receptor_charges " + parpars.get("s") + "\n";
}
float ligand_charge_scaling_factor = 1.0f;
if (parpars.get("t") != CommandlineParser::NOT_FOUND)
{
ligand_charge_scaling_factor = parpars.get("t").toFloat();
configuration_string += "scale_ligand_charges " + parpars.get("t") + "\n";
}
String protein_file_name = parpars.get("rec");
if (protein_file_name == CommandlineParser::NOT_FOUND)
{
Log.error() << "Missing protein file name." << endl;
return 1;
}
configuration_string += "protein_file_name " + protein_file_name + "\n";
String ligand_file_name = parpars.get("lig");
if (ligand_file_name == CommandlineParser::NOT_FOUND)
{
Log.error() << "Missing ligand file name." << endl;
return 1;
}
configuration_string += "ligand_file_name " + ligand_file_name + "\n";
if (verbosity > 0)
{
Log.info() << "Initializing residue checker." << endl;
}
FragmentDB db("fragments/Fragments.db");
ResidueChecker check(db);
time_t rawtime;
time(&rawtime);
String time_string("start: " + String(asctime(localtime(&rawtime))));
// now load the molecules and assign radii and charges depending on
// what the user wants
System system;
PDBFile protein_file(protein_file_name);
protein_file >> system;
protein_file.close();
Molecule* protein = system.getMolecule(0);
if (verbosity > 0)
{
Log.info() << "Normalizing names (protein)." << endl;
}
system.apply(db.normalize_names);
if (verbosity > 0)
{
Log.info() << "Building bonds (protein)." << endl;
}
system.apply(db.build_bonds);
HINFile ligand_hin_file;
ligand_hin_file.open(ligand_file_name);
ligand_hin_file >> system;
ligand_hin_file.close();
Molecule* ligand = system.getMolecule(1);
// Read and apply charge rules
String charge_rule_file_name = parpars.get("cr");
if (charge_rule_file_name == CommandlineParser::NOT_FOUND)
{
charge_rule_file_name = "solvation/PARSE+ions.rul";
}
else
{
configuration_string += "use_charge_rules " + charge_rule_file_name + "\n";
tmp = path.find(charge_rule_file_name);
if (tmp != "")
{
charge_rule_file_name = tmp;
}
if (verbosity > 0)
{
Log.info() << "Using " << charge_rule_file_name << " as charge rule file" << endl;
}
INIFile charge_ini(charge_rule_file_name);
charge_ini.read();
ChargeRuleProcessor charge_rules(charge_ini);
system.apply(charge_rules);
}
// Read and apply polar charge rules
String polar_radius_rule_file_name = parpars.get("pr");
if (polar_radius_rule_file_name == CommandlineParser::NOT_FOUND)
{
polar_radius_rule_file_name = "solvation/PARSE+ions.rul";
}
else
{
configuration_string += "use_polar_radius_rules " + polar_radius_rule_file_name + "\n";
tmp = path.find(polar_radius_rule_file_name);
if (tmp != "")
{
polar_radius_rule_file_name = tmp;
}
if (verbosity > 0)
{
Log.info() << "Using " << polar_radius_rule_file_name << " as polar radius rule file" << endl;
}
INIFile radius_ini(polar_radius_rule_file_name);
radius_ini.read();
RadiusRuleProcessor radius_rules(radius_ini);
system.apply(radius_rules);
}
if (verbosity > 8)
{
Log.info() << "system statistics:" << endl;
Log.info() << "molecules: " << system.countMolecules() << endl;
Log.info() << "proteins: " << system.countProteins() << endl;
Log.info() << "fragments: " << system.countFragments() << endl;
Log.info() << "atoms: " << system.countAtoms() << endl;
}
// check for uassigned type names
AtomIterator it;
int count = 0;
for (it = system.beginAtom(); +it; ++it)
{
count++;
if (it->getElement().getSymbol() == "?")
{
Log.info() << "Got symbol \"?\": " << it->getFullName() << endl;
}
if (it->getCharge() > 8.0)
{
Log.error() << "Mysterious charge: " << it->getCharge() << "\t"
<< it->getFullName() << "\t" << count << "\t" << it->getElement().getSymbol() << endl;
}
}
// scale charges
if (verbosity > 0)
{
Log.info() << "Scaling receptor charges by " << receptor_charge_scaling_factor << endl;
}
if (parpars.has("s"))
{
for (it = protein->beginAtom(); +it; ++it)
{
it->setCharge(it->getCharge() * receptor_charge_scaling_factor);
}
}
if (verbosity > 0)
{
Log.info() << "Scaling ligand charges by " << ligand_charge_scaling_factor << endl;
}
if (parpars.has("t"))
{
for (it = ligand->beginAtom(); +it; ++it)
{
it->setCharge(it->getCharge() * ligand_charge_scaling_factor);
}
}
String options_file_name = parpars.get("op");
if (options_file_name != CommandlineParser::NOT_FOUND)
{
options.readOptionFile(options_file_name);
configuration_string += "read_options_file " + options_file_name;
}
String lj_parameter_file_name = parpars.get("lj");
if (lj_parameter_file_name == CommandlineParser::NOT_FOUND)
{
lj_parameter_file_name = "Amber/amber94gly.ini";
}
else
{
configuration_string = configuration_string + "lj_parameter_file_name " + lj_parameter_file_name;
}
options.set(VanDerWaalsSlick::Option::LENNARD_JONES_FILE, lj_parameter_file_name);
if (parpars.has("u"))
{
options.setBool(PolarSolvation::Option::UNITE_ATOMS, true);
cout << "Uniting atoms." << endl;
configuration_string += "unite_atoms true\n";
}
else
{
options.setBool(PolarSolvation::Option::UNITE_ATOMS, false);
cout << "Not uniting atoms." << endl;
}
String nonpolar_radius_rule_file_name = parpars.get("n");
if (nonpolar_radius_rule_file_name == CommandlineParser::NOT_FOUND)
{
nonpolar_radius_rule_file_name = "solvation/bondi.rul";
}
else
{
cout << "Using " << nonpolar_radius_rule_file_name << " for nonpolar radii" << endl;
configuration_string += "use_nonpolar_radius_rules " + nonpolar_radius_rule_file_name + "\n";
options.setBool(NonpolarSolvation::Option::NONPOLAR_OVERWRITE_RADII, true);
options.set(NonpolarSolvation::Option::NONPOLAR_RADIUS_RULES, nonpolar_radius_rule_file_name);
}
float score = 0.0f;
if (!parpars.has("S"))
{
configuration_string = configuration_string + "calculate_energy\n";
SLICKEnergy slick(*protein, *ligand, options);
score = slick.calculateScore();
cout << endl << "SLICK/energy is " << score << " kJ/mol" << endl;
if (verbosity > 1)
{
cout << endl << "Scores (w/o coefficients)" << endl << endl;
cout << "Hydrogen bonds " << slick.getHydrogenBondScore() << endl;
cout << "CHPI " << slick.getCHPIScore() << endl;
cout << "VanDerWaalsSlick " << slick.getVDWScore() << endl;
cout << "Nonpolar solvation " << slick.getNonpolarSolvationScore() << endl;
cout << "Polar Solvation " << slick.getPolarSolvationScore() << endl;
}
#ifdef OLD_DATAFILE_FORMAT
String dat_file_name;
String component;
File datfile;
component = "SLICKenergy";
dat_file_name = component + ".dat";
datfile.open(dat_file_name, std::ios::out);
datfile << protein_file_name << " " << ligand_file_name << " " << score << " " << component << endl;
datfile.close();
component = "HB";
dat_file_name = component + ".dat";
datfile.open(dat_file_name, std::ios::out);
datfile << protein_file_name << " " << ligand_file_name << " " << slick.getHydrogenBondScore()
<< " " << component << endl;
datfile.close();
component = "CHPISlick";
dat_file_name = component + ".dat";
datfile.open(dat_file_name, std::ios::out);
datfile << protein_file_name << " " << ligand_file_name << " " << slick.getCHPIScore()
<< " " << component << endl;
datfile.close();
component = "VDW5";
dat_file_name = component + ".dat";
datfile.open(dat_file_name, std::ios::out);
datfile << protein_file_name << " " << ligand_file_name << " " << slick.getVDWScore()
<< " " << component << endl;
datfile.close();
component = "NONPOLAR2";
dat_file_name = component + ".dat";
datfile.open(dat_file_name, std::ios::out);
datfile << protein_file_name << " " << ligand_file_name << " " << slick.getNonpolarSolvationScore()
<< " " << component << endl;
datfile.close();
component = "DESOLV4";
dat_file_name = component + ".dat";
datfile.open(dat_file_name, std::ios::out);
datfile << protein_file_name << " " << ligand_file_name << " " << slick.getPolarSolvationScore()
<< " " << component << endl;
datfile.close();
#endif
time(&rawtime);
time_string = time_string + String("stop: " + String(asctime(localtime(&rawtime))));
if (parpars.has("log"))
{
File logfile("SLICKenergy.log", std::ios::out);
logfile << configuration_string << endl;
logfile << time_string << endl;
logfile.close();
}
}
if (!parpars.has("E"))
{
configuration_string = configuration_string + "calculate_score\n";
SLICKScore slick(*protein, *ligand, options);
score = slick.calculateScore();
cout << endl << "SLICK/score is " << score << " (arb. units)" << endl;
if (verbosity > 1)
{
cout << endl << "Scores (w/o coefficients)" << endl << endl;
cout << "Hydrogen bonds " << slick.getHydrogenBondScore() << endl;
cout << "CHPI " << slick.getCHPIScore() << endl;
cout << "VanDerWaalsSlick " << slick.getVDWScore() << endl;
cout << "Electrostatic int. " << slick.getPolarSolvationScore() << endl;
}
#ifdef OLD_DATAFILE_FORMAT
String dat_file_name;
String component;
File datfile;
component = "SLICKenergy";
dat_file_name = component + ".dat";
datfile.open(dat_file_name, std::ios::out);
datfile << protein_file_name << " " << ligand_file_name << " " << score << " " << component << endl;
datfile.close();
component = "HB";
dat_file_name = component + ".dat";
datfile.open(dat_file_name, std::ios::out);
datfile << protein_file_name << " " << ligand_file_name << " " << slick.getHydrogenBondScore() << " " << component << endl;
datfile.close();
component = "CHPISlick";
dat_file_name = component + ".dat";
datfile.open(dat_file_name, std::ios::out);
datfile << protein_file_name << " " << ligand_file_name << " " << slick.getCHPIScore() << " " << component << endl;
datfile.close();
component = "VDW5";
dat_file_name = component + ".dat";
datfile.open(dat_file_name, std::ios::out);
datfile << protein_file_name << " " << ligand_file_name << " " << slick.getVDWScore() << " " << component << endl;
datfile.close();
component = "COULOMB";
dat_file_name = component + ".dat";
datfile.open(dat_file_name, std::ios::out);
datfile << protein_file_name << " " << ligand_file_name << " " << slick.getPolarSolvationScore() << " " << component << endl;
datfile.close();
#endif
time(&rawtime);
time_string = time_string + String("stop: " + String(asctime(localtime(&rawtime))));
if (parpars.has("log"))
{
File logfile("SLICKscore.log", std::ios::out);
logfile << configuration_string << endl;
logfile << time_string << endl;
logfile.close();
}
}
}
CHECK(AntechamberFile::AntechamberFile(const String& filename, File::OpenMode open_mode)) // checking for default mode: reading AntechamberFile f(BALL_TEST_DATA_PATH(AntechamberFile_test1.ac)); TEST_EQUAL(f.isValid(), true) RESULT CHECK(AntechamberFile::read(System& system)) AntechamberFile f(BALL_TEST_DATA_PATH(AntechamberFile_test2.ac)); System S; f.read(S); f.close(); TEST_EQUAL(S.countAtoms(), 2) AtomIterator it = S.beginAtom(); TEST_EQUAL(it->getElement().getSymbol(), "H") TEST_REAL_EQUAL(it->getPosition().x, 0.0) TEST_REAL_EQUAL(it->getPosition().y, 1.0) TEST_REAL_EQUAL(it->getPosition().z, 2.0) it++; TEST_EQUAL(it->getElement().getSymbol(), "O") TEST_REAL_EQUAL(it->getPosition().x, 3.0) TEST_REAL_EQUAL(it->getPosition().y, 4.0) TEST_REAL_EQUAL(it->getPosition().z, 5.0) RESULT CHECK(AntechamberFile::read(System& system)) AntechamberFile f(BALL_TEST_DATA_PATH(AntechamberFile_test1.ac)); System S; f.read(S);
double Polarity::updateScore()
{
score_ = 0.0;
//float val = 0.0;
//float distance;
//float R1;
//float R2;
const HashGrid3<Atom*>* hashgrid = scoring_function_->getHashGrid();
int radius = 1;
Size no_neighbor_cells = (Size)pow((double)(radius*2+1), 3); // radius of 1 cell == > 3 cells on each axis
double total_sum = 0;
AtomPairVector::const_iterator it;
for (AtomIterator it = scoring_function_->getLigand()->beginAtom(); +it; it++)
{
int no_positive_contacts = 0;
int no_negative_contacts = 0;
bool ligandatom_is_lipophilic = isLipophilic_(&*it);
if (!ligandatom_is_lipophilic)
{
continue;
}
const HashGridBox3<Atom*>* box = hashgrid->getBox(it->getPosition());
// ligand atom lies outside of grid
if (!box) continue;
Position pos_x, pos_y, pos_z;
hashgrid->getIndices(*box, pos_x, pos_y, pos_z);
// indices in HashGrid, where the search for interacting target atoms should begin ( != position of ligand atom)
int i = ((int)pos_x)-radius; if (i < 0){i = 0; }
int j0 = ((int)pos_y)-radius; if (j0 < 0){j0 = 0; }
int k0 = ((int)pos_z)-radius; if (k0 < 0){k0 = 0; }
int x_size = (int)hashgrid->getSizeX();
int y_size = (int)hashgrid->getSizeY();
int z_size = (int)hashgrid->getSizeZ();
for (; i <= pos_x+radius && i < x_size; i++)
{
for (int j = j0; j <= pos_y+radius && j < y_size; j++)
{
for (int k = k0; k <= pos_z+radius && k < z_size; k++)
{
const HashGridBox3<Atom*>* box = hashgrid->getBox(i, j, k);
if (!box->isEmpty())
{
double cell_score = 0;
for (HashGridBox3 < Atom* > ::ConstDataIterator d_it = box->beginData(); d_it != box->endData(); d_it++)
{
if (isBackboneAtom_(*d_it)) continue;
bool rec_polar = isPolar_(*d_it);
bool rec_lipophilic = 0;
if (!rec_polar) rec_lipophilic = isLipophilic_(*d_it);
if (!rec_polar && ! rec_lipophilic) continue;
double distance = ((*d_it)->getPosition()-it->getPosition()).getLength();
if (distance > (*d_it)->getElement().getVanDerWaalsRadius()+it->getElement().getVanDerWaalsRadius()+1.5) continue;
double val;
if (distance > 1) val = 1/distance;
else val = 1;
// lipophilic--lipophilic interaction; else polar rec. -- lipophilic ligand atom
if (rec_lipophilic)
{
val *= -1;
}
cell_score += val;
total_sum += val;
if (scoring_function_->storeInteractionsEnabled())
{
val = scaleScore(val);
it->addInteraction(*d_it, "pol", val);
(*d_it)->addInteraction(&*it, "pol", val);
}
}
if (cell_score < -0.1) no_positive_contacts++;
else if (cell_score > 0.1) no_negative_contacts++;
}
// if there is no neighboring receptor atom, there will be water ...
// else if(i!=pos_x||j!=pos_y||k!=pos_z)
// {
// if(ligandatom_is_lipophilic)
// {
// no_negative_contacts++;
// double scaled_atom_score = 1.0/no_neighbor_cells;
// scaleScore(scaled_atom_score);
// total_sum += scaled_atom_score;
// it->addInteraction("pol",scaled_atom_score);
// }
// }
}
}
}
score_ += (no_negative_contacts-no_positive_contacts)/((double)no_neighbor_cells);
//cout<<it->getFullName()<<" : "<<no_negative_contacts<<", "<<no_positive_contacts<<" "<<(no_negative_contacts-no_positive_contacts)/((double)no_neighbor_cells)<<endl;
}
// scaleScore();
// cout<<"polarity: total sum="<<total_sum<<endl;
// cout<<"polarity: score="<<score_<<endl;
// return score_;
return getScaledScore();
}