public static ApproximatePeptide FromPeptide(Peptide peptide)
{
var dihedralAngles = AminoAcidAngleMeasurer.MeasureAngles(peptide);
var approximateAminoAcids = new List <ApproximatedAminoAcid>();
foreach (var aminoAcid in peptide.AminoAcids)
{
PdbAminoAcidAtomNamer.AssignNames(aminoAcid);
var nitrogen = aminoAcid.GetAtomFromName("N");
var carbonAlpha = aminoAcid.GetAtomFromName("CA");
var carbon = aminoAcid.GetAtomFromName("C");
var aminoAcidDihedralAngles = dihedralAngles[aminoAcid];
var approximateAminoAcid = new ApproximatedAminoAcid(aminoAcid.Name, aminoAcid.SequenceNumber)
{
NitrogenPosition = nitrogen.Position,
CarbonAlphaPosition = carbonAlpha.Position,
CarbonPosition = carbon.Position,
OmegaAngle = aminoAcidDihedralAngles.Omega,
PhiAngle = aminoAcidDihedralAngles.Phi,
PsiAngle = aminoAcidDihedralAngles.Psi,
IsFrozen = true
};
approximateAminoAcids.Add(approximateAminoAcid);
}
return(new ApproximatePeptide(approximateAminoAcids));
}
public void MeasureAminoAcidDistances(string pdbFilePath, int sequenceNumber1, int sequenceNumber2)
{
var pdb = PdbReader.ReadFile(pdbFilePath);
var firstChain = pdb.Models.First().Chains.First();
var aminoAcidAngles = AminoAcidAngleMeasurer.MeasureAngles(firstChain);
var aminoAcid1 = firstChain.AminoAcids.Find(x => x.SequenceNumber == sequenceNumber1);
var aminoAcid2 = firstChain.AminoAcids.Find(x => x.SequenceNumber == sequenceNumber2);
var aminoAcid1Angles = aminoAcidAngles[aminoAcid1];
var aminoAcid2Angles = aminoAcidAngles[aminoAcid2];
var carbonAlphaDistance = aminoAcid1.GetAtomFromName("CA").Position
.DistanceTo(aminoAcid2.GetAtomFromName("CA").Position);
Console.WriteLine("Carbon alpha distance: " + carbonAlphaDistance);
Console.WriteLine($"Amino acid {sequenceNumber1} ({aminoAcid1.Name}) angles: {aminoAcid1Angles}");
Console.WriteLine($"Amino acid {sequenceNumber2} ({aminoAcid2.Name}) angles: {aminoAcid2Angles}");
var carbonAlphaCarbonDistance = aminoAcid1.GetAtomFromName("CA").Position
.DistanceTo(aminoAcid1.GetAtomFromName("C").Position);
Console.WriteLine($"Carbon alpha-Carbon distance: {carbonAlphaCarbonDistance}");
var carbonNitrogenDistance = aminoAcid1.GetAtomFromName("C").Position
.DistanceTo(aminoAcid2.GetAtomFromName("N").Position);
Console.WriteLine($"Carbon-Nitrogen distance: {carbonNitrogenDistance}");
}
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));
}
/// <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);
}
public void DihedralAnglesConverge()
{
var targetPhi = 40.To(Unit.Degree);
var targetPsi = -10.To(Unit.Degree);
var approximatePeptide = ApproximatePeptideBuilder.FromSequence(new [] { AminoAcidName.Alanine, AminoAcidName.Alanine, AminoAcidName.Alanine }, 1);
approximatePeptide.UpdatePositions();
var startAngles = AminoAcidAngleMeasurer.MeasureAngles(approximatePeptide);
var simulationSettings = new ApproximatePeptideSimulationSettings
{
SimulationTime = 500.To(SIPrefix.Femto, Unit.Second),
TimeStep = 2.To(SIPrefix.Femto, Unit.Second),
ResetAtomVelocityAfterEachTimestep = true,
UseCompactingForce = false
};
var ramachandranPlotDistribution = new RamachandranPlotFixedDistribution(AminoAcidName.Alanine, new UnitPoint2D(targetPhi, targetPsi));
var distributionSource = new RamachandranPlotDistributionFixedSource(ramachandranPlotDistribution);
var sut = new RamachandranForceCalculator(distributionSource);
var simulator = new ApproximatePeptideFoldingSimulator(
approximatePeptide,
simulationSettings,
new CompactingForceCalculator(),
sut,
new BondForceCalculator());
var angleHistory = new List <AminoAcidAngles>();
var simulationEndedWaitHandle = new ManualResetEvent(false);
simulator.SimulationCompleted += (sender, args) => simulationEndedWaitHandle.Set();
simulator.TimestepCompleted += (sender, args) =>
{
var angles = AminoAcidAngleMeasurer.MeasureAngles(args.PeptideCopy);
var midAminoAcid = args.PeptideCopy.AminoAcids[1];
angleHistory.Add(angles[midAminoAcid]);
};
simulator.StartSimulation();
simulationEndedWaitHandle.WaitOne();
File.WriteAllLines(@"G:\Projects\HumanGenome\angles.csv",
angleHistory.Select(angle => $"{angle.Omega.In(Unit.Degree).ToString(CultureInfo.InvariantCulture)};" +
$"{angle.Phi.In(Unit.Degree).ToString(CultureInfo.InvariantCulture)};" +
$"{angle.Psi.In(Unit.Degree).ToString(CultureInfo.InvariantCulture)}"));
var finalAngles = AminoAcidAngleMeasurer.MeasureAngles(approximatePeptide);
var middleAminoAcid = approximatePeptide.AminoAcids[1];
Assert.That((finalAngles[middleAminoAcid].Phi - targetPhi).Abs(),
Is.LessThan((startAngles[middleAminoAcid].Phi - targetPhi).Abs()));
Assert.That((finalAngles[middleAminoAcid].Psi - targetPsi).Abs(),
Is.LessThan((startAngles[middleAminoAcid].Psi - targetPsi).Abs()));
}
public void Psi90PlusMeasuredCorrectly()
{
var peptide = PeptideBuilder.PeptideFromString("GG");
var firstAminoAcid = peptide.AminoAcids.First();
var lastAminoAcid = peptide.AminoAcids.Last();
PdbAminoAcidAtomNamer.AssignNames(firstAminoAcid);
PdbAminoAcidAtomNamer.AssignNames(lastAminoAcid);
var N1 = firstAminoAcid.GetAtomFromName("N");
var Ca1 = firstAminoAcid.GetAtomFromName("CA");
var C1 = firstAminoAcid.GetAtomFromName("C");
var N2 = lastAminoAcid.GetAtomFromName("N");
var Ca2 = lastAminoAcid.GetAtomFromName("CA");
var C2 = lastAminoAcid.GetAtomFromName("C");
N1.Position = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 0, 0, 0);
N1.IsPositionFixed = true;
Ca1.Position = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 100, 0, 0);
Ca1.IsPositionFixed = true;
C1.Position = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 100, 100, 0);
C1.IsPositionFixed = true;
N2.Position = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 100, 100, 100);
N2.IsPositionFixed = true;
Ca2.Position = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 200, 100, 100);
Ca2.IsPositionFixed = true;
C2.Position = new UnitPoint3D(SIPrefix.Pico, Unit.Meter, 200, 200, 100);
C2.IsPositionFixed = true;
var measurements = AminoAcidAngleMeasurer.MeasureAngles(peptide);
Assert.That(measurements.ContainsKey(firstAminoAcid));
Assert.That(measurements.ContainsKey(lastAminoAcid));
var firstAngles = measurements[firstAminoAcid];
var lastAngles = measurements[lastAminoAcid];
Assert.That(firstAngles.Omega, Is.Null);
Assert.That(firstAngles.Phi, Is.Null);
Assert.That(firstAngles.Psi, Is.Not.Null);
Assert.That(firstAngles.Psi.In(Unit.Degree), Is.EqualTo(90));
Assert.That(lastAngles.Omega, Is.Not.Null);
Assert.That(lastAngles.Omega.In(Unit.Degree), Is.EqualTo(90));
}
private static Dictionary <AminoAcidReference, AminoAcidAngles> MeasureDihedralAngles(string pdbFilename)
{
var result = PdbReader.ReadFile(pdbFilename);
var angleMeasurements = new Dictionary <AminoAcidReference, AminoAcidAngles>();
foreach (var chain in result.Models.First().Chains)
{
var angleMeasurement = AminoAcidAngleMeasurer.MeasureAngles(chain);
foreach (var kvp in angleMeasurement)
{
angleMeasurements.Add(kvp.Key, kvp.Value);
}
}
return(angleMeasurements);
}
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 CarbonAlphaDistancesMatchRealMeasurements()
{
var aminoAcid1 = new ApproximatedAminoAcid(AminoAcidName.Valine, 90)
{
OmegaAngle = 179.9.To(Unit.Degree),
PhiAngle = -35.9.To(Unit.Degree),
PsiAngle = -52.0.To(Unit.Degree)
};
var aminoAcid2 = new ApproximatedAminoAcid(AminoAcidName.Alanine, 91)
{
OmegaAngle = 179.9.To(Unit.Degree),
PhiAngle = -63.5.To(Unit.Degree),
PsiAngle = -59.7.To(Unit.Degree)
};
var peptide = new[] { aminoAcid1, aminoAcid2 };
ApproximateAminoAcidPositioner.Position(peptide, new UnitPoint3D(Unit.Meter, 0, 0, 0));
var carbonAlphaCarbonDistance = aminoAcid1.CarbonAlphaPosition
.DistanceTo(aminoAcid1.CarbonPosition);
Assert.That(carbonAlphaCarbonDistance.In(SIPrefix.Pico, Unit.Meter), Is.EqualTo(154).Within(0.1));
var carbonNitrogenDistance = aminoAcid1.CarbonPosition
.DistanceTo(aminoAcid2.NitrogenPosition);
Assert.That(carbonNitrogenDistance.In(SIPrefix.Pico, Unit.Meter), Is.EqualTo(152).Within(0.1));
var aminoAcidAngles = AminoAcidAngleMeasurer.MeasureAngles(new ApproximatePeptide(peptide));
Assert.That(aminoAcidAngles[aminoAcid1].Psi.Value - aminoAcid1.PsiAngle.Value, Is.EqualTo(0).Within(0.1));
Assert.That(aminoAcidAngles[aminoAcid2].Phi.Value - aminoAcid2.PhiAngle.Value, Is.EqualTo(0).Within(0.1));
// The bond length vary because we use theoretical bond length, which do not exactly match real bond lengths
//Assert.That(
// aminoAcid1.CarbonAlphaPosition.DistanceTo(aminoAcid2.CarbonAlphaPosition).In(SIPrefix.Pico, Unit.Meter),
// Is.EqualTo(380.3).Within(0.1));
}
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));
}
