void optimize()
{
if (use_selection)
{
Log.info() << "SELECT: " << selection << endl;
Selector selector(selection);
S.apply(selector);
// count selected vs. unselected atoms
Size selected = 0;
AtomConstIterator ai = S.beginAtom();
for (; +ai; ++ai)
{
selected += (ai->isSelected() ? 1 : 0);
}
Log.info() << "selected " << selected << " out of " << S.countAtoms() << " atoms." << endl;
}
// minimize
Log.info() << "starting minimization";
EnergyMinimizer* minimizer;
if (sd_minimizer)
{
minimizer = new SteepestDescentMinimizer(amber);
}
else
{
minimizer = new ConjugateGradientMinimizer(amber);
}
if (verbose)
{
minimizer->setEnergyOutputFrequency(1);
}
else
{
minimizer->setEnergyOutputFrequency(20);
}
minimizer->setEnergyDifferenceBound(1e-9);
minimizer->setMaxSameEnergy(20);
minimizer->setMaxGradient(max_gradient);
minimizer->minimize(max_iterations);
Log.info() << "minimization complete" << endl;
Log.info() << "final gradient: " << amber.getRMSGradient() << " kJ/mol A" << endl;
S.deselect();
amber.updateEnergy();
Log.info() << "final energy: " << amber.getEnergy() << " kJ/mol" << endl;
// dump the minimizer and force field options
// for documentation purposes
amber.options.dump(Log);
minimizer->options.dump(Log);
Log.info() << "done." << endl;
}
void singlePoint()
{
double energy = amber.updateEnergy();
amber.updateForces();
Gradient grad;
grad.set(amber.getAtoms());
grad.normalize();
Log.info() << "single point energy: " << energy << " kJ/mol" << endl;
Log.info() << " - stretch :" << amber.getStretchEnergy() << " kJ/mol" << endl;
Log.info() << " - bend :" << amber.getBendEnergy() << " kJ/mol" << endl;
Log.info() << " - torsion :" << amber.getTorsionEnergy() << " kJ/mol" << endl;
Log.info() << " - VdW :" << amber.getVdWEnergy() << " kJ/mol" << endl;
Log.info() << " - electrostatic:" << amber.getESEnergy() << " kJ/mol" << endl;
Log.info() << "grad: " << grad.rms << endl;
}
void checkStructures()
{
// fragment DB
if (frag_db == 0)
{
frag_db = new FragmentDB;
}
Log.info() << "system contains " << S.countAtoms() << " atoms." << endl;
// building bonds
S.apply(frag_db->build_bonds);
// checking residues
Log.info() << "checking system" << endl;
ResidueChecker check(*frag_db);
S.apply(check);
// Check residue energies
double energy_limit = 500.0;
S.deselect();
amber.setup(S);
ResidueIterator it = S.beginResidue();
for (; +it; ++it)
{
it->select();
amber.updateEnergy();
double residue_energy = amber.getStretchEnergy() + amber.getBendEnergy()
+ amber.getVdWEnergy();
if (residue_energy > energy_limit)
{
Log.info() << "suspicious energies in residue " << it->getFullName() << ":" << it->getID() << " " << residue_energy
<< " kJ/mol (bend: " << amber.getBendEnergy() << " kJ/mol, stretch: " << amber.getStretchEnergy()
<< " kJ/mol, vdW: " << amber.getVdWEnergy() << " kJ/mol)" << endl;
}
it->deselect();
double quality = std::max(0.0, std::min(1.0, (energy_limit - residue_energy) / energy_limit));
for (PDBAtomIterator ai = it->beginPDBAtom(); +ai; ++ai)
{
ai->setOccupancy(quality);
}
}
}
int main(int argc, char** argv)
{
Log.setPrefix(cout, "[%T] ");
Log.setPrefix(cerr, "[%T] ERROR: ");
// issue a usage hint if called without parameters
if (argc != 3)
{
Log << argv[0] << " <PDB infile> <PDB outfile>" << endl;
return 1;
}
// open a PDB file with the name of the first argument
PDBFile file(argv[1]);
if (!file)
{
// if file does not exist: complain and abort
Log.error() << "error opening " << argv[1] << " for input." << endl;
return 2;
}
// create a system and read the contents of the PDB file
System S;
file >> S;
file.close();
// print the number of atoms read from the file
Log << "read " << S.countAtoms() << " atoms." << endl;
// now we open a fragment database
Log << "reading fragment DB..." << endl;
FragmentDB fragment_db("");
// and normalize the atom names, i.e. we convert different
// naming standards to the PDB naming scheme - just in case!
Log << "normalizing names..." << endl;
S.apply(fragment_db.normalize_names);
// now we add any missing hydrogens to the residues
// the data on the hydrogen positions stems from the
// fragment database. However the hydrogen positions
// created in this way are only good estimates
Log << "creating missing atoms..." << endl;
S.apply(fragment_db.add_hydrogens);
Log << "added " << fragment_db.add_hydrogens.getNumberOfInsertedAtoms()
<< " atoms" << endl;
// now we create the bonds between the atoms (PDB files hardly
// ever contain a complete set of CONECT records)
Log << "building bonds..." << endl;
S.apply(fragment_db.build_bonds);
// now we check whether the model we built is consistent
// The ResidueChecker checks for charges, bond lengths,
// and missing atoms
Log << "checking the built model..." << endl;
ResidueChecker checker(fragment_db);
S.apply(checker);
// now we create an AMBER force field
Log << "setting up force field..." << endl;
AmberFF FF;
// we then select all hydrogens (element(H))
// using a specialized processor (Selector)
S.deselect();
FF.setup(S);
Selector selector("element(H)");
S.apply(selector);
// just for curiosity: check how many atoms we are going
// to optimize
Log << "optimizing " << FF.getNumberOfMovableAtoms() << " out of " << S.countAtoms() << " atoms" << endl;
// now we create a minimizer object that uses a conjugate
// gradient algorithm to optimize the atom positions
ConjugateGradientMinimizer minimizer;
// calculate the total energy of the system
float initial_energy = FF.updateEnergy();
Log << "initial energy: " << initial_energy << " kJ/mol" << endl;
// initialize the minimizer and perform (up to)
// 1000 optimization steps
minimizer.setup(FF);
minimizer.setEnergyOutputFrequency(1);
minimizer.minimize(50);
// calculate the terminal energy and print it
float terminal_energy = FF.getEnergy();
Log << "energy before/after minimization: " << initial_energy << "/" << terminal_energy << " kJ/mol" << endl;
// write the optimized structure to a file whose
// name is given as the second command line argument
Log << "writing PBD file " << argv[2] << endl;
file.open(argv[2], ios::out);
file << S;
file.close();
// done.
return 0;
}
int main(int argc, char** argv)
{
if (argc != 3)
{
Log.error() << argv[0] << " <pdb file A> <pdb file B>" << endl;
return 1;
}
// open the first PDB file
PDBFile pdb(argv[1]);
if (pdb.bad())
{
// if the file could not be opened, print error message and exit
Log.error() << "cannot open PBD file " << argv[1] << endl;
return 2;
}
// read the contents of the file A into a system
System A;
pdb >> A;
pdb.close();
// open the second PDB file
pdb.open(argv[2]);
if (pdb.bad())
{
// if the file could not be opened, print error message and exit
Log.error() << "cannot open PBD file " << argv[2] << endl;
return 2;
}
// read the contents of the file B into a system
System B;
pdb >> B;
pdb.close();
// normalize the names and build all bonds
Log.info() << "normalizing names and building bonds..." << endl;
FragmentDB db("");
A.apply(db.normalize_names);
A.apply(db.build_bonds);
B.apply(db.normalize_names);
B.apply(db.build_bonds);
// calculate the atomic contact energies of A and B
float ACE_A = calculateACE(A);
float ACE_B = calculateACE(B);
// calculate the electrostatic energies of A and B
AmberFF amber;
amber.options[AmberFF::Option::ASSIGN_CHARGES] = "true";
amber.options[AmberFF::Option::OVERWRITE_CHARGES] = "true";
amber.setup(A);
amber.updateEnergy();
float ES_A = amber.getESEnergy();
float C_A = calculateCoulomb(A);
amber.setup(B);
amber.updateEnergy();
float ES_B = amber.getESEnergy();
float C_B = calculateCoulomb(B);
// finally, join the to systems into a single system
cout << "atoms in A: " << A.countAtoms() << endl;
cout << "atoms in B: " << B.countAtoms() << endl;
A.splice(B);
cout << "final atoms: " << A.countAtoms() << endl;
float ACE_AB = calculateACE(A);
amber.setup(A);
amber.updateEnergy();
float ES_AB = amber.getESEnergy();
float C_AB = calculateCoulomb(A);
// print the resulting energies
cout << "ES energy of A: " << ES_A << endl;
cout << "ES energy of B: " << ES_B << endl;
cout << "ES energy of AB:" << ES_AB << endl;
cout << "C energy of A: " << C_A << endl;
cout << "C energy of B: " << C_B << endl;
cout << "C energy of AB:" << C_AB << endl;
cout << "change in atomic contact energy on binding: "
<< (ACE_AB - ACE_A - ACE_B) << " kJ/mol" << endl;
cout << "change in electrostatic energy on binding: "
<< (ES_AB - ES_A - ES_B) << " kJ/mol" << endl;
cout << "total binding free energy: "
<< (ACE_AB - ACE_A - ACE_B) + (ES_AB - ES_A - ES_B) << " kJ/mol" << endl;
// done
return 0;
}