/
PeptideFactory.java
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/
PeptideFactory.java
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import java.util.*;
import java.io.*;
import com.google.common.collect.*;
import org.apache.commons.math3.geometry.euclidean.threed.*;
import org.jgrapht.*;
import org.jgrapht.graph.*;
import org.jgrapht.alg.*;
import java.util.concurrent.*;
/**
* This class creates peptides.
*/
public class PeptideFactory
{
/** This class is not instantiable. */
private PeptideFactory()
{
throw new IllegalArgumentException("not instantiable");
}
/**
* Sets hairpin angles for the given peptide.
* This method expects a single D-proline followed by a glycine.
* @param peptide the peptide to adjust the angles for
* @return the adjusted peptide
*/
public static Peptide setHairpinAngles(Peptide peptide)
{
// figure out which residues to adjust
Residue prolineResidue = null;
Residue glycineResidue = null;
Integer prolineResidueIndex = null;
Integer glycineResidueIndex = null;
for (int i=0; i < peptide.sequence.size(); i++)
{
Residue residue = peptide.sequence.get(i);
if ( residue.aminoAcid == AminoAcid.DPRO )
{
if ( prolineResidue != null )
throw new IllegalArgumentException("found two D-prolines");
prolineResidue = residue;
glycineResidue = peptide.sequence.get(i+1);
prolineResidueIndex = i;
glycineResidueIndex = i+1;
if ( glycineResidue.aminoAcid != AminoAcid.GLY )
throw new IllegalArgumentException("glycine expected after D-proline");
i++;
}
}
if ( prolineResidue == null || glycineResidue == null )
throw new NullPointerException("hairpin not found");
// set the dihedral angles
// these angles are from the Balaram crystal structure
Peptide newPeptide = BackboneMutator.setOmega (peptide, prolineResidueIndex, 175.0);
newPeptide = BackboneMutator.setPhiPsi(peptide, prolineResidueIndex, 53.0, -132.0);
newPeptide = RotamerMutator.setChis (peptide, prolineResidueIndex, ImmutableList.of(-22.0, 32.0, -29.0));
newPeptide = BackboneMutator.setOmega (peptide, glycineResidueIndex, -178.0);
newPeptide = BackboneMutator.setPhiPsi(peptide, glycineResidueIndex, -96.0, 9.0);
// set hairpin flags
List<Residue> newSequence = new ArrayList<>(newPeptide.sequence.size());
for (int i=0; i < newPeptide.sequence.size(); i++)
{
Residue residue = newPeptide.sequence.get(i);
if ( i == prolineResidueIndex || i == glycineResidueIndex )
newSequence.add(residue.setHairpin(true));
else
newSequence.add(residue.setHairpin(false));
}
newPeptide = new Peptide(newPeptide.name, newPeptide.contents, newPeptide.connectivity, newSequence, newPeptide.energyBreakdown);
return newPeptide;
}
/**
* Builds a peptide given a sequence of ProtoAminoAcids.
* @param inputSequence the requested sequence specified in the N to C direction
* @return the Peptide that embodies the geometry and metadata of the sequence
*/
public static Peptide createPeptide(List<ProtoAminoAcid> inputSequence)
{
if ( inputSequence.size() < 2 )
throw new IllegalArgumentException("A peptide must have at least two residues in it.");
// create temporary lists for creating a new Residue
List<AminoAcid> aminoAcids = new LinkedList<>();
List<ProtoTorsion> omegas = new LinkedList<>();
List<ProtoTorsion> phis = new LinkedList<>();
List<ProtoTorsion> psis = new LinkedList<>();
List<List<ProtoTorsion>> chis = new LinkedList<>();
List<Atom> HNs = new LinkedList<>();
List<Atom> Ns = new LinkedList<>();
List<Atom> Os = new LinkedList<>();
List<Atom> Cs = new LinkedList<>();
List<Atom> CAs = new LinkedList<>();
List<Atom> HAs = new LinkedList<>();
List<String> descriptions = new LinkedList<>();
List<Pair<Atom,Atom>> prochiralConnections = new LinkedList<>();
List<List<Atom>> atoms = new LinkedList<>();
List<Boolean> isHairpins = new LinkedList<>();
// for Molecule part of new Peptide
String newName = "";
List<Atom> newContents = new LinkedList<>();
SimpleWeightedGraph<Atom,DefaultWeightedEdge> newConnectivity = new SimpleWeightedGraph<>(DefaultWeightedEdge.class);
Set<Pair<Atom,Atom>> newBonds = new HashSet<>();
// keep track of connections so new bonds can be formed
List<Pair<Atom,Atom>> NStickyConnections = new LinkedList<>();
List<Pair<Atom,Atom>> CStickyConnections = new LinkedList<>();
List<Pair<Atom,Atom>> newConnections = new LinkedList<>();
List<Pair<Integer,Integer>> newIndexConnections = new LinkedList<>();
// build peptide in N to C direction
for (int i=0; i < inputSequence.size(); i++)
{
// get data for this amino acid
ProtoAminoAcid p = inputSequence.get(i).shift(i+1);
AminoAcid tempAminoAcid = p.residue.aminoAcid;
ProtoTorsion tempOmega = p.residue.omega;
ProtoTorsion tempPhi = p.residue.phi;
ProtoTorsion tempPsi = p.residue.psi;
List<ProtoTorsion> tempChis = p.residue.chis;
Atom tempHN = p.residue.HN;
Atom tempN = p.residue.N;
Atom tempO = p.residue.O;
Atom tempC = p.residue.C;
Atom tempCA = p.residue.CA;
Atom tempHA = p.residue.HA;
String tempDescription = p.residue.description;
Pair<Atom,Atom> tempNStickyConnection = p.NStickyConnection;
Pair<Atom,Atom> tempCStickyConnection = p.CStickyConnection;
Pair<Atom,Atom> tempProchiralConnection = p.residue.prochiralConnection;
List<Atom> tempAtoms = p.residue.atoms;
boolean tempIsHairpin = false;
Molecule tempMolecule = p.molecule;
// append to name
if ( i == 0 )
newName += String.format("%5s", tempAminoAcid.shortName);
else
newName += String.format(" - %5s", tempAminoAcid.shortName);
aminoAcids.add(tempAminoAcid);
// add relevant atoms from this ProtoAminoAcid
tempAtoms = new LinkedList<>(tempAtoms);
if ( i > 0 )
{
// delete N-terminal cap
Atom keepAtom = tempNStickyConnection.getFirst();
Atom deleteAtom = tempNStickyConnection.getSecond();
Set<Atom> toBeDeleted = tempMolecule.getHalfGraph(keepAtom, deleteAtom);
tempAtoms.removeAll(toBeDeleted);
}
if ( i < inputSequence.size() - 1 )
{
// delete C-terminal cap
Atom keepAtom = tempCStickyConnection.getFirst();
Atom deleteAtom = tempCStickyConnection.getSecond();
Set<Atom> toBeDeleted = tempMolecule.getHalfGraph(keepAtom, deleteAtom);
tempAtoms.removeAll(toBeDeleted);
}
newContents.addAll(tempAtoms); // the atoms in the whole peptide
atoms.add(tempAtoms); // list of the atoms in each residue
// add relevant connectivity from each ProtoAminoAcid
for (DefaultWeightedEdge e : tempMolecule.connectivity.edgeSet())
{
// assumes all edge weights are 1
Atom fromAtom = tempMolecule.connectivity.getEdgeSource(e);
Atom toAtom = tempMolecule.connectivity.getEdgeTarget(e);
if ( tempAtoms.contains(fromAtom) && tempAtoms.contains(toAtom) )
newBonds.add( new Pair<Atom,Atom>(fromAtom, toAtom) );
}
// form new bond
NStickyConnections.add(tempNStickyConnection);
CStickyConnections.add(tempCStickyConnection);
if ( i > 0 ) // no need to form a bond on the first residue
{
// join the C sticky atom of the previous residue
// to the N sticky atom of the current residue
// sticky atom connections are defined as ordered pairs: (keep, delete)
Atom lastCStickyAtom = CStickyConnections.get(i-1).getFirst();
Atom thisNStickyAtom = NStickyConnections.get(i).getFirst();
Pair<Atom,Atom> newConnection = new Pair<>(lastCStickyAtom, thisNStickyAtom);
//System.out.println(newContents.indexOf(lastCStickyAtom)+1);
//System.out.println(newContents.indexOf(thisNStickyAtom)+1);
// mark this in a list of all the new peptide bonds
newConnections.add(newConnection);
// mark for addition to connectivity graph
newBonds.add(newConnection);
// specify the new connections by atom number because atoms will be moved
// indices: 0, 1, 2, ..., N
Integer fromAtomIndex = newContents.indexOf(lastCStickyAtom);
Integer toAtomIndex = newContents.indexOf(thisNStickyAtom);
Pair<Integer,Integer> newIndexPair = new Pair<>(fromAtomIndex, toAtomIndex);
newIndexConnections.add(newIndexPair);
}
// update backbone angles
if ( i == 0 )
{
// copy ProtoTorsions for first residue
omegas.add(tempOmega);
phis.add(tempPhi);
psis.add(tempPsi);
}
else if ( i > 0 )
{
// get last ProtoTorsions
ProtoTorsion lastPsi = psis.remove(psis.size()-1);
// update ProtoTorsions for previous residue
ProtoTorsion newLastPsi = new ProtoTorsion(lastPsi.atom1, lastPsi.atom2, lastPsi.atom3, tempOmega.atom3);
psis.add(newLastPsi);
// update ProtoTorsions for current residue
ProtoTorsion newOmega = new ProtoTorsion(lastPsi.atom2, lastPsi.atom3, tempOmega.atom3, tempOmega.atom4);
ProtoTorsion newPhi = new ProtoTorsion(lastPsi.atom3, tempPhi.atom2, tempPhi.atom3, tempPhi.atom4);
omegas.add(newOmega);
phis.add(newPhi);
psis.add(tempPsi);
}
// add sidechain torsion angles
chis.add(tempChis);
// update special atom fields
HNs.add(tempHN);
Ns.add(tempN);
Os.add(tempO);
Cs.add(tempC);
CAs.add(tempCA);
HAs.add(tempHA);
// add other fields
descriptions.add(tempDescription);
prochiralConnections.add(tempProchiralConnection);
isHairpins.add(tempIsHairpin);
}
// create new connectivity graph
for (Atom a : newContents)
newConnectivity.addVertex(a);
for (Pair<Atom,Atom> p : newBonds)
{
// assumes all edges have a weight of 1.0
Atom fromAtom = p.getFirst();
Atom toAtom = p.getSecond();
DefaultWeightedEdge e = newConnectivity.addEdge(fromAtom, toAtom);
newConnectivity.setEdgeWeight(e, 1.0);
//System.out.println( (newContents.indexOf(fromAtom)+1) + " -- " + (newContents.indexOf(toAtom)+1) );
}
// create residue objects to make a Sequence
List<Residue> sequence = new LinkedList<>();
for (int i=0; i < inputSequence.size(); i++)
{
Residue residue = new Residue(aminoAcids.get(i), omegas.get(i), phis.get(i), psis.get(i), chis.get(i),
HNs.get(i), Ns.get(i), Os.get(i), Cs.get(i), CAs.get(i), HAs.get(i),
descriptions.get(i), prochiralConnections.get(i), atoms.get(i), isHairpins.get(i));
sequence.add(residue);
}
sequence = ImmutableList.copyOf(sequence);
// create new peptide object
Peptide peptide = new Peptide(newName, newContents, newConnectivity, sequence, EnergyBreakdown.BLANK);
// adjust distances
for (Pair<Integer,Integer> bond : newIndexConnections)
{
Atom fromAtom = peptide.contents.get(bond.getFirst());
Atom toAtom = peptide.contents.get(bond.getSecond());
peptide = peptide.setMolecule( peptide.setDistance(fromAtom,toAtom,1.32) );
}
// set peptide bonds to sp2
for (int i=0; i < inputSequence.size(); i++)
{
// set amide carbonyl carbon to sp2
Residue r = peptide.sequence.get(i);
ProtoTorsion omega = r.omega;
Atom fromAtom = omega.atom2;
Atom toAtom = omega.atom3;
peptide = peptide.setMolecule( peptide.set_sp2(fromAtom,toAtom) );
// set amide nitrogen to sp2
r = peptide.sequence.get(i);
omega = r.omega;
fromAtom = omega.atom3;
toAtom = omega.atom2;
// only force (amide substituent 1 -- N -- amide substituent 2) angle to 120
// if this is not a proline
if ( r.aminoAcid.isProline() )
peptide = peptide.setMolecule( peptide.set_sp2(fromAtom,toAtom,false) );
else
peptide = peptide.setMolecule( peptide.set_sp2(fromAtom,toAtom, true) );
}
// set all backbone torsions to trans
for (int i=0; i < inputSequence.size(); i++)
peptide = BackboneMutator.setOmega(peptide, i, 180.0);
return peptide;
}
/** For testing. */
public static void main(String[] args)
{
DatabaseLoader.go();
List<ProtoAminoAcid> sequence = ProtoAminoAcidDatabase.getSpecificSequence("arg","met","standard_ala","gly","d_proline", "gly", "phe", "val", "hd", "l_pro");
Peptide peptide = PeptideFactory.createPeptide(sequence);
for (int i=0; i < peptide.sequence.size(); i++)
{
peptide = BackboneMutator.mutateOmega(peptide, i);
peptide = BackboneMutator.mutatePhiPsi(peptide, i);
peptide = RotamerMutator.mutateChis(peptide, i);
}
peptide = PeptideFactory.setHairpinAngles(peptide);
GaussianInputFile f = new GaussianInputFile(peptide);
f.write("test_peptides/test.gjf");
//peptide = BackboneMutator.mutateOmega(peptide, 1);
//peptide = BackboneMutator.mutatePhiPsi(peptide, peptide.sequence.get(1));
//f = new GaussianInputFile(peptide);
//f.write("test_peptides/test2.gjf");
}
}