public void ForceDirectionAsExpected()
{
var approximatePeptide = new ApproximatePeptide(new []
{
new ApproximatedAminoAcid(AminoAcidName.Alanine, 1)
{
NitrogenPosition = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, -150, -150, 0),
CarbonAlphaPosition = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 0, -150, 0),
CarbonPosition = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 0, 0, 0)
},
new ApproximatedAminoAcid(AminoAcidName.Alanine, 2)
{
NitrogenPosition = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 150, 0, 0),
CarbonAlphaPosition = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 150, 0, 150),
CarbonPosition = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 300, 0, 150)
}
});
var angles = AminoAcidAngleMeasurer.MeasureAngles(approximatePeptide);
var ramachandranPlotDistribution = new RamachandranPlotFixedDistribution(AminoAcidName.Alanine, new UnitPoint2D(Unit.Degree, -90, -20));
var distributionSource = new RamachandranPlotDistributionFixedSource(ramachandranPlotDistribution);
var sut = new RamachandranForceCalculator(distributionSource);
var forces = sut.Calculate(approximatePeptide);
var aminoAcid1Forces = forces[approximatePeptide.AminoAcids[0]];
var aminoAcid2Forces = forces[approximatePeptide.AminoAcids[1]];
Assert.That(aminoAcid1Forces.CarbonAlphaForce.In(Unit.Newton).Z, Is.LessThan(0));
Assert.That(aminoAcid1Forces.CarbonForce.Magnitude().In(Unit.Newton), Is.EqualTo(0).Within(1e-6));
Assert.That(aminoAcid2Forces.NitrogenForce.Magnitude().In(Unit.Newton), Is.EqualTo(0).Within(1e-6));
Assert.That(aminoAcid2Forces.CarbonAlphaForce.In(Unit.Newton).Y, Is.GreaterThan(0));
}
public void VolumeAsExpected()
{
var aa1 = new ApproximatedAminoAcid(AminoAcidName.Alanine, 1);
var aa2 = new ApproximatedAminoAcid(AminoAcidName.Alanine, 2);
var aa3 = new ApproximatedAminoAcid(AminoAcidName.Alanine, 3);
var peptide = new ApproximatePeptide(new List <ApproximatedAminoAcid> {
aa1, aa2, aa3
});
// Set positions
aa1.NitrogenPosition = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 0, 0, 0);
aa1.CarbonAlphaPosition = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 1, 0, 0);
aa1.CarbonPosition = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 1, 1, 0);
aa2.NitrogenPosition = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 0, 1, 0);
aa2.CarbonAlphaPosition = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 0, 1, 1);
aa2.CarbonPosition = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 1, 1, 1);
aa3.NitrogenPosition = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 1, 0, 1);
aa3.CarbonAlphaPosition = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 0, 0, 1);
aa3.CarbonPosition = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 0.5, 0.5, 0.5);
var result = CompactnessMeasurer.Measure(peptide);
var volume = result.Volume.Value;
var picoMultiplier = SIPrefix.Pico.GetMultiplier();
var cubicPicoMultiplier = picoMultiplier * picoMultiplier * picoMultiplier;
Assert.That(volume / cubicPicoMultiplier, Is.EqualTo(1).Within(1e-6));
}
public SimulationTimestepCompleteEventArgs(UnitValue t, ApproximatePeptide peptide)
: this(t)
{
PeptideCopy = peptide.DeepClone();
Atoms = AtomExtractor.FromApproximatePeptide(peptide);
Atoms.ForEach(atom => atom.IsBackbone = true);
}
public static CompactnessMeasurerResult Measure(ApproximatePeptide peptide)
{
var vertices = ToVertices(peptide.AminoAcids);
var convexHull = ConvexHull.Create(vertices);
var volume = CalculateVolume(convexHull.Result);
var convexHullGraph = ToGraph(convexHull.Result);
return(new CompactnessMeasurerResult(volume, convexHullGraph));
}
public ApproximatePeptide Simulate(
IList <AminoAcidName> aminoAcidSequence,
MultiLevelGrowingFoldingSimulatorSettings settings)
{
var peptide = new ApproximatePeptide();
var aminoAcidStack = new Stack <AminoAcidName>(aminoAcidSequence.Reverse()); // See MultiLevelGrowingFoldingSimulatorStudy.StackInit
RecursiveAddAndPositionNewAminoAcid(peptide, aminoAcidStack, settings);
FoldSecondaryStructure(peptide);
return(peptide);
}
public static ApproximatePeptideFoldingSimulator Create(ApproximatePeptide peptide,
ApproximatePeptideSimulationSettings simulationSettings,
string ramachadranDataDirectory)
{
var compactnessForceCalculator = new CompactingForceCalculator();
var ramachandranPlotDistributionSource = new RamachandranPlotGradientDistributionFileSource(ramachadranDataDirectory);
var ramachadranForceCalculator = new RamachandranForceCalculator(ramachandranPlotDistributionSource);
var bondForceCalculator = new BondForceCalculator();
return(new ApproximatePeptideFoldingSimulator(peptide,
simulationSettings,
compactnessForceCalculator,
ramachadranForceCalculator,
bondForceCalculator));
}
public ApproximatePeptideFoldingSimulator(ApproximatePeptide peptide,
ApproximatePeptideSimulationSettings simulationSettings,
CompactingForceCalculator compactnessForceCalculator,
RamachandranForceCalculator ramachandranForceCalculator,
BondForceCalculator bondForceCalculator)
{
this.simulationSettings = simulationSettings;
this.compactnessForceCalculator = compactnessForceCalculator;
this.ramachandranForceCalculator = ramachandranForceCalculator;
this.bondForceCalculator = bondForceCalculator;
Peptide = peptide;
if (peptide.AminoAcids.Count <= 3)
{
simulationSettings.UseCompactingForce = false; // Cannot be done
}
}
private void RecursiveAddAndPositionNewAminoAcid(
ApproximatePeptide peptide,
Stack <AminoAcidName> aminoAcidQueue,
MultiLevelGrowingFoldingSimulatorSettings settings)
{
var aminoAcidName = aminoAcidQueue.Pop();
var lastAminoAcid = peptide.AminoAcids.LastOrDefault();
var lastPosition = lastAminoAcid?.CarbonAlphaPosition ?? new UnitPoint3D(Unit.Meter, 0, 0, 0);
var influencingAminoAcids = peptide.AminoAcids
.Where(x => x.CarbonAlphaPosition.DistanceTo(lastPosition) < settings.InfluenceHorizont)
.ToList();
var ramachandranPlot = ramachandranPlotSource.Get(aminoAcidName);
var sequenceNumber = lastAminoAcid?.SequenceNumber + 1 ?? 0;
var isTimeForSecondaryStructureFolding =
sequenceNumber % settings.SecondaryStructureFoldingFrequency == 0;
if (isTimeForSecondaryStructureFolding)
{
FoldSecondaryStructure(peptide);
}
var remainingPositionAttempts = settings.PositioningAttempts;
do
{
try
{
var aminoAcid = new ApproximatedAminoAcid(aminoAcidName, sequenceNumber);
PositionAminoAcid(aminoAcid, lastAminoAcid, ramachandranPlot, influencingAminoAcids, settings);
peptide.Add(aminoAcid);
RecursiveAddAndPositionNewAminoAcid(peptide, aminoAcidQueue, settings);
return;
}
catch (AminoAcidCannotBePositionedException)
{
remainingPositionAttempts--;
}
} while (remainingPositionAttempts > 0);
aminoAcidQueue.Push(aminoAcidName);
throw new AminoAcidCannotBePositionedException(aminoAcidName, sequenceNumber);
}
public static List <Atom> FromApproximatePeptide(ApproximatePeptide peptide)
{
var atoms = new List <Atom>();
foreach (var aminoAcid in peptide.AminoAcids)
{
var nitrogenAtom = Atom.FromStableIsotope(ElementName.Nitrogen);
nitrogenAtom.Position = aminoAcid.NitrogenPosition;
var carbonAlphaAtom = Atom.FromStableIsotope(ElementName.Carbon);
carbonAlphaAtom.Position = aminoAcid.CarbonAlphaPosition;
var carbonAtom = Atom.FromStableIsotope(ElementName.Carbon);
carbonAtom.Position = aminoAcid.CarbonPosition;
atoms.Add(nitrogenAtom);
atoms.Add(carbonAlphaAtom);
atoms.Add(carbonAtom);
}
return(atoms);
}
public void AminoAcidPositioningTest()
{
var aminoAcid1 = new ApproximatedAminoAcid(AminoAcidName.Glycine, 1)
{
OmegaAngle = 0.To(Unit.Degree),
PhiAngle = 0.To(Unit.Degree),
PsiAngle = -120.To(Unit.Degree)
};
var aminoAcid2 = new ApproximatedAminoAcid(AminoAcidName.Glycine, 2)
{
OmegaAngle = 10.To(Unit.Degree),
PhiAngle = -70.To(Unit.Degree),
PsiAngle = 0.To(Unit.Degree)
};
var peptide = new ApproximatePeptide(new [] { aminoAcid1, aminoAcid2 });
var angles = AminoAcidAngleMeasurer.MeasureAngles(peptide);
var aminoAcid1Angles = angles[aminoAcid1];
var aminoAcid2Angles = angles[aminoAcid2];
Assert.That(aminoAcid1Angles.Psi.In(Unit.Radians), Is.EqualTo(aminoAcid1.PsiAngle.In(Unit.Radians)).Within(1e-9));
Assert.That(aminoAcid2Angles.Omega.In(Unit.Radians), Is.EqualTo(aminoAcid2.OmegaAngle.In(Unit.Radians)).Within(1e-9));
Assert.That(aminoAcid2Angles.Phi.In(Unit.Radians), Is.EqualTo(aminoAcid2.PhiAngle.In(Unit.Radians)).Within(1e-9));
}
public void AtomPositionsAsExpected()
{
var aminoAcid1 = new ApproximatedAminoAcid(AminoAcidName.Valine, 90)
{
OmegaAngle = 45.To(Unit.Degree),
PhiAngle = -60.To(Unit.Degree),
PsiAngle = 90.To(Unit.Degree)
};
var aminoAcid2 = new ApproximatedAminoAcid(AminoAcidName.Alanine, 91)
{
OmegaAngle = 0.To(Unit.Degree),
PhiAngle = -90.To(Unit.Degree),
PsiAngle = 90.To(Unit.Degree)
};
var peptide = new ApproximatePeptide(new[] { aminoAcid1, aminoAcid2 });
ApproximateAminoAcidPositioner.Position(peptide.AminoAcids, new UnitPoint3D(Unit.Meter, 0, 0, 0));
var angles = AminoAcidAngleMeasurer.MeasureAngles(peptide);
Assert.That(angles[aminoAcid1].Psi.In(Unit.Degree), Is.EqualTo(aminoAcid1.PsiAngle.In(Unit.Degree)).Within(1));
Assert.That(angles[aminoAcid2].Omega.In(Unit.Degree), Is.EqualTo(aminoAcid2.OmegaAngle.In(Unit.Degree)).Within(1));
Assert.That(angles[aminoAcid2].Phi.In(Unit.Degree), Is.EqualTo(aminoAcid2.PhiAngle.In(Unit.Degree)).Within(1));
//Assert.That(
// aminoAcid1.NitrogenPosition.DistanceTo(new UnitPoint3D(Unit.Meter, 0, 0, 0)).In(SIPrefix.Pico, Unit.Meter),
// Is.EqualTo(0).Within(1e-3));
//Assert.That(
// aminoAcid1.CarbonAlphaPosition.DistanceTo(new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 152, 0, 0)).In(SIPrefix.Pico, Unit.Meter),
// Is.EqualTo(0).Within(1e-3));
//Assert.That(
// aminoAcid1.CarbonPosition.DistanceTo(new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 152, 154, 0)).In(SIPrefix.Pico, Unit.Meter),
// Is.EqualTo(0).Within(1e-3));
//Assert.That(
// aminoAcid2.NitrogenPosition.DistanceTo(new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 152, 154, 152)).In(SIPrefix.Pico, Unit.Meter),
// Is.EqualTo(0).Within(1e-3));
}
public Dictionary <ApproximatedAminoAcid, ApproximateAminoAcidForces> Calculate(ApproximatePeptide peptide)
{
// VALIDATED: Forces point in the right direction and restore expected bond length
var bondForces = peptide.AminoAcids.ToDictionary(aa => aa, aa => new ApproximateAminoAcidForces());
for (var aminoAcidIdx = 0; aminoAcidIdx < peptide.AminoAcids.Count; aminoAcidIdx++)
{
var aminoAcid = peptide.AminoAcids[aminoAcidIdx];
var previousAminoAcid = aminoAcidIdx > 0
? peptide.AminoAcids[aminoAcidIdx - 1]
: null;
CalculateBondLengthForces(previousAminoAcid, aminoAcid, bondForces);
CalculateBondAngleForces(previousAminoAcid, aminoAcid, bondForces);
}
return(bondForces);
}
public ApproximatePeptideCompleter(ApproximatePeptide approximatePeptide)
{
this.approximatePeptide = approximatePeptide;
}
private void FoldSecondaryStructure(ApproximatePeptide peptide)
{
// Do nothing for now
}
public static Dictionary <ApproximatedAminoAcid, AminoAcidAngles> MeasureAngles(ApproximatePeptide peptide)
{
var measurements = new Dictionary <ApproximatedAminoAcid, AminoAcidAngles>();
AminoAcidAngles lastAngles = null;
UnitPoint3D lastNitrogenPosition = null;
UnitPoint3D lastCarbonAlphaPosition = null;
UnitPoint3D lastCarbonPosition = null;
foreach (var aminoAcid in peptide.AminoAcids)
{
var nitrogenPosition = aminoAcid.NitrogenPosition;
var carbonAlphaPosition = aminoAcid.CarbonAlphaPosition;
var carbonPosition = aminoAcid.CarbonPosition;
if (lastAngles != null &&
lastNitrogenPosition != null &&
lastCarbonAlphaPosition != null &&
lastCarbonPosition != null &&
nitrogenPosition != null)
{
var psi = DihedralAngleCalculator.Calculate(
lastNitrogenPosition,
lastCarbonAlphaPosition,
lastCarbonPosition,
nitrogenPosition);
lastAngles.Psi = psi;
}
UnitValue omega = null;
if (lastCarbonAlphaPosition != null &&
lastCarbonPosition != null &&
nitrogenPosition != null &&
carbonAlphaPosition != null)
{
omega = DihedralAngleCalculator.Calculate(
lastCarbonAlphaPosition,
lastCarbonPosition,
nitrogenPosition,
carbonAlphaPosition);
}
UnitValue phi = null;
if (lastCarbonPosition != null &&
nitrogenPosition != null &&
carbonAlphaPosition != null &&
carbonPosition != null)
{
phi = DihedralAngleCalculator.Calculate(
lastCarbonPosition,
nitrogenPosition,
carbonAlphaPosition,
carbonPosition);
}
var angles = new AminoAcidAngles
{
Omega = omega,
Phi = phi
};
measurements.Add(aminoAcid, angles);
lastNitrogenPosition = nitrogenPosition;
lastCarbonAlphaPosition = carbonAlphaPosition;
lastCarbonPosition = carbonPosition;
lastAngles = angles;
}
return(measurements);
}
/// <summary>
/// Use Ramachmadran plot position of an amino acid for pushing it
/// to keep it away from prohibited zones.
/// </summary>
public Dictionary <ApproximatedAminoAcid, ApproximateAminoAcidForces> Calculate(ApproximatePeptide peptide)
{
var forceDictionary = new Dictionary <ApproximatedAminoAcid, ApproximateAminoAcidForces>();
var aminoAcidAnglesDictionary = AminoAcidAngleMeasurer.MeasureAngles(peptide);
for (var aminoAcidIdx = 0; aminoAcidIdx < peptide.AminoAcids.Count; aminoAcidIdx++)
{
var aminoAcid = peptide.AminoAcids[aminoAcidIdx];
var previousAminoAcid = aminoAcidIdx > 0 ? peptide.AminoAcids[aminoAcidIdx - 1] : null;
var nextAminoAcid = aminoAcidIdx + 1 < peptide.AminoAcids.Count
? peptide.AminoAcids[aminoAcidIdx + 1]
: null;
var plotDistribution = distributionSource.GetDistribution(aminoAcid.Name);
var aminoAcidAngles = aminoAcidAnglesDictionary[aminoAcid];
if (aminoAcidAngles.Omega != null && !aminoAcidAngles.Omega.Value.IsNaN())
{
ApplyOmegaDeviationForce(previousAminoAcid, aminoAcid, aminoAcidAngles, forceDictionary);
}
if (aminoAcidAngles.Phi != null && aminoAcidAngles.Psi != null)
{
var plotGradient = plotDistribution.GetPhiPsiVector(aminoAcidAngles.Phi, aminoAcidAngles.Psi).In(Unit.Degree);
var phiDeviation = plotGradient.X;
var psiDeviation = plotGradient.Y;
ApplyPhiDeviationForce(previousAminoAcid, aminoAcid, forceDictionary, phiDeviation);
ApplyPsiDeviationForce(aminoAcid, nextAminoAcid, forceDictionary, psiDeviation);
}
}
return(forceDictionary);
}
