private void PositionAminoAcid(
ApproximatedAminoAcid aminoAcid,
ApproximatedAminoAcid lastAminoAcid,
RamachandranPlot ramachandranPlot,
List <ApproximatedAminoAcid> influencingAminoAcids,
MultiLevelGrowingFoldingSimulatorSettings settings)
{
var influencingCenter = CalculateCenter(influencingAminoAcids);
var positionAttempt = 1;
do
{
var aminoAcidAngles = ramachandranPlot.GetRandomPhiPsi();
aminoAcid.OmegaAngle = aminoAcidAngles.Omega;
aminoAcid.PhiAngle = aminoAcidAngles.Phi;
aminoAcid.PsiAngle = aminoAcidAngles.Psi;
ApproximateAminoAcidPositioner.PositionAminoAcid(aminoAcid, lastAminoAcid, new UnitPoint3D(Unit.Meter, 0, 0, 0));
// Note: Clashing distance was determined using MultiLevelGrowingFoldingSimulatorStudy.MeasureAverageAminoAcidDistance
var isClashingWithAnyInfluencingAminoAcid = influencingAminoAcids
.Any(otherAminoAcid => otherAminoAcid.CarbonAlphaPosition.DistanceTo(aminoAcid.CarbonAlphaPosition).In(SIPrefix.Nano, Unit.Meter) < 1.0);
if (isClashingWithAnyInfluencingAminoAcid)
{
positionAttempt++;
continue;
}
if (lastAminoAcid != null && influencingAminoAcids.Count > 0)
{
var isTooFarAway = aminoAcid.CarbonAlphaPosition.DistanceTo(influencingCenter) > lastAminoAcid.CarbonAlphaPosition.DistanceTo(influencingCenter) &&
aminoAcid.CarbonAlphaPosition.DistanceTo(influencingCenter) > 0.8 * settings.InfluenceHorizont;
if (isTooFarAway)
{
positionAttempt++;
continue;
}
}
return;
} while (positionAttempt < settings.PositioningAttempts);
throw new AminoAcidCannotBePositionedException(aminoAcid.Name, aminoAcid.SequenceNumber);
}
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));
}
public void GenerateProteins()
{
var angleInverseDistributions = LoadInverseAngleDistributions();
var pdbId = "1a2b";
var aminoAcidSequence = ReadAminoAcidSequenceFromPositionFile($@"G:\Projects\HumanGenome\Protein-PDBs\HumanProteins\AminoAcidPositions\pdb{pdbId}_model000.csv");
var distanceMapsDirectory = @"G:\Projects\HumanGenome\generatedProteins\DistanceMaps";
var positionFilesDirectory = @"G:\Projects\HumanGenome\generatedProteins\PositionFiles";
var distanceMean = 380;
var distanceSigma = 4;
var iterations = 1000;
for (int iteration = 0; iteration < iterations; iteration++)
{
var aminoAcidPositions = new List <Point3D> {
new Point3D(0, 0, 0)
};
var lastAminoAcidLetter = aminoAcidSequence[0];
for (var aminoAcidIdx = 1; aminoAcidIdx < aminoAcidSequence.Count; aminoAcidIdx++)
{
var aminoAcidLetter = aminoAcidSequence[aminoAcidIdx];
var distance = StaticRandom.NextGaussian(distanceMean, distanceSigma);
if (aminoAcidPositions.Count < 2)
{
aminoAcidPositions.Add(new Point3D(distance, 0, 0));
lastAminoAcidLetter = aminoAcidLetter;
continue;
}
var angleInverseDistribution = angleInverseDistributions[lastAminoAcidLetter];
var angleInRadians = angleInverseDistribution.ValueAtX(StaticRandom.Rng.NextDouble());
var lastPosition = aminoAcidPositions.Last().To(SIPrefix.Pico, Unit.Meter);
var vector1 = aminoAcidPositions[aminoAcidIdx - 2].VectorTo(aminoAcidPositions[aminoAcidIdx - 1]);
var vector2 = aminoAcidIdx >= 3
? aminoAcidPositions[aminoAcidIdx - 3].VectorTo(aminoAcidPositions[aminoAcidIdx - 2])
: new Vector3D(0, 1, 0);
var bestPositionedPoint = ApproximateAminoAcidPositioner.CalculateAtomPosition(
lastPosition,
vector1,
vector2,
distance.To(SIPrefix.Pico, Unit.Meter),
angleInRadians.To(Unit.Radians),
(2 * Math.PI * (StaticRandom.Rng.NextDouble() - 0.5)).To(Unit.Radians));
var isColliding = CollidesWithExistingPositions(bestPositionedPoint, aminoAcidPositions, out var distanceToClosest);
var bestDistanceToClosest = distanceToClosest;
const int MaxPositionIterations = 3;
var positionIteration = 0;
while (isColliding && positionIteration < MaxPositionIterations)
{
positionIteration++;
var pointCandidate = ApproximateAminoAcidPositioner.CalculateAtomPosition(
lastPosition,
vector1,
vector2,
distance.To(SIPrefix.Pico, Unit.Meter),
angleInRadians.To(Unit.Radians),
(2 * Math.PI * (StaticRandom.Rng.NextDouble() - 0.5)).To(Unit.Radians));
isColliding = CollidesWithExistingPositions(bestPositionedPoint, aminoAcidPositions, out distanceToClosest);
if (!isColliding)
{
bestPositionedPoint = pointCandidate;
break;
}
if (distanceToClosest > bestDistanceToClosest)
{
bestPositionedPoint = pointCandidate;
bestDistanceToClosest = distanceToClosest;
}
}
aminoAcidPositions.Add(bestPositionedPoint.In(SIPrefix.Pico, Unit.Meter));
lastAminoAcidLetter = aminoAcidLetter;
}
var filenameBase = $"pdb{pdbId}_gen{iteration}";
var distanceMap = DistanceMapGenerator.Generate(aminoAcidPositions);
distanceMap.Save(Path.Combine(distanceMapsDirectory, filenameBase + ".png"));
File.WriteAllLines(
Path.Combine(positionFilesDirectory, filenameBase + ".csv"),
Enumerable.Range(0, aminoAcidSequence.Count)
.Select(idx => $"{aminoAcidSequence[idx]};{aminoAcidPositions[idx].ToString()}"));
}
}
public void UpdatePositions()
{
ApproximateAminoAcidPositioner.Position(AminoAcids, new UnitPoint3D(Unit.Meter, 0, 0, 0));
}
