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Molecule.py
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Molecule.py
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from rdkit import Chem
from rdkit.Chem import AllChem
from rdkit.Chem.rdchem import Mol
import numpy as np
import numpy.linalg as la
from numpy.typing import NDArray
import os
import sys
from dataclasses import dataclass
import argparse
from RingFinder import RingFinder
from typing import List
@dataclass
class Ellipse:
center: NDArray
square_matrix: NDArray
eigen_values: NDArray
eigen_vectors: NDArray
axes_magnitudes: NDArray
axes: NDArray
points: NDArray
atom_idxs: List[int]
@dataclass
class ProgramInput:
expandAtom: bool
smiles: str
fragment: bool
numberNeighbors: int
mergeLength: int
@dataclass
class MoleculeOutput:
mol: Mol
ellipsis: [Ellipse]
def generate_3d_conformation(mol: Mol) -> Mol:
mol = Chem.AddHs(mol)
AllChem.EmbedMolecule(mol)
AllChem.MMFFOptimizeMolecule(mol)
return mol
def molecule_points(mol: Mol, expandAtom, atom_idxs=None) -> NDArray:
conformer = mol.GetConformer()
coordinates = []
atoms = []
if atom_idxs is None:
atoms = mol.GetAtoms()
else:
for atom_idx in atom_idxs:
atom = mol.GetAtomWithIdx(atom_idx)
atoms.append(atom)
for atom in atoms:
x = atom.GetAtomicNum()
if x > 1:
index = atom.GetIdx()
if expandAtom:
coordinate = conformer.GetAtomPosition(index)
r = Chem.GetPeriodicTable().GetRvdw(x)
coordinate.x = coordinate.x + r;
coordinates.append(coordinate)
coordinate = conformer.GetAtomPosition(index)
coordinate.x = coordinate.x - r;
coordinates.append(coordinate)
coordinate = conformer.GetAtomPosition(index)
coordinate.y = coordinate.y + r;
coordinates.append(coordinate)
coordinate = conformer.GetAtomPosition(index)
coordinate.y = coordinate.y - r;
coordinates.append(coordinate)
coordinate = conformer.GetAtomPosition(index)
coordinate.z = coordinate.z + r;
coordinates.append(coordinate)
coordinate = conformer.GetAtomPosition(index)
coordinate.z = coordinate.z - r;
coordinates.append(coordinate)
else:
coordinate = conformer.GetAtomPosition(index)
coordinates.append(coordinate)
return np.asarray(coordinates)
# from https://gist.github.com/Gabriel-p/4ddd31422a88e7cdf953
def mvee(points, tol=0.0001) -> [NDArray,NDArray]:
"""
Finds the ellipse equation in "center form"
(x-c).T * A * (x-c) = 1
"""
N, d = points.shape
Q = np.column_stack((points, np.ones(N))).T
err = tol+1.0
u = np.ones(N)/N
while err > tol:
# assert u.sum() == 1 # invariant
X = np.dot(np.dot(Q, np.diag(u)), Q.T)
M = np.diag(np.dot(np.dot(Q.T, la.inv(X)), Q))
jdx = np.argmax(M)
step_size = (M[jdx]-d-1.0)/((d+1)*(M[jdx]-1.0))
new_u = (1-step_size)*u
new_u[jdx] += step_size
err = la.norm(new_u-u)
u = new_u
c = np.dot(u, points)
A = la.inv(np.dot(np.dot(points.T, np.diag(u)), points)
- np.multiply.outer(c, c))/d
return A, c
def quadratic_to_parametric(center: NDArray, A: NDArray) -> Ellipse:
# eigenvalues and eigenvectors using SVD
# see https://en.wikipedia.org/wiki/Singular_value_decomposition
# and https://laurentlessard.com/teaching/cs524/slides/11%20-%20quadratic%20forms%20and%20ellipsoids.pdf
# For square symmetric A = U.D.VT matrix U = V
# and Eigen values of A are singular values in D
# Columns of U (rows of VT) are Eigen vectors of A
U, D, VT = la.svd(A)
axes_magnitudes = 1.0/np.sqrt(D)
small = [x < 1 for x in axes_magnitudes]
if all(small) == True:
return ValueError
# hack to multiply by row instead of column
axes = VT * axes_magnitudes[:, np.newaxis]
ellipse = Ellipse(center = center, square_matrix = A, eigen_values = D, eigen_vectors = U, axes_magnitudes = axes_magnitudes, axes = axes, points = None, atom_idxs=None)
return ellipse
def print_pymol_ellipse(moleculeOutput: MoleculeOutput, base: str) -> None:
mol = moleculeOutput.mol
block = Chem.MolToMolBlock(mol)
out_file = f'{base}.sdf'
with open(out_file, 'wt') as fh:
fh.write(block)
full_sd_path = os.getcwd() + os.path.sep + out_file;
py_script = f'{base}.py'
with open(py_script, 'wt') as fh:
fh.write('from pymol.cgo import *\n')
fh.write("cmd.delete('all')\n")
fh.write(f"cmd.load('{full_sd_path}')\n")
for ellipse_idx, ellipse in enumerate(moleculeOutput.ellipsis):
center = ellipse.center
mag = ellipse.axes_magnitudes
rot = ellipse.eigen_vectors
drawCommand = f'tmp{ellipse_idx} = drawEllipsoid([0.85, 0.85, 1.00] '
for i in range(3):
drawCommand = drawCommand + f', {center[i]}'
for i in range(3):
drawCommand = drawCommand + f', {mag[i]}'
for i in range(3):
for j in range(3):
drawCommand = drawCommand + f', {rot[i][j]}'
drawCommand = drawCommand + ')'
fh.write(drawCommand)
fh.write('\n')
fh.write(f"cmd.load_cgo(tmp{ellipse_idx}, 'ellipsoid-cgo{ellipse_idx}')\n")
fh.write(f"cmd.set('cgo_transparency', 0.5, 'ellipsoid-cgo{ellipse_idx}')\n")
fh.write(f"obj{ellipse_idx} = [\n BEGIN, LINES, \n COLOR, 0, 1.0, 0, \n")
# write axes
for i in range(0,3):
fh.write(f'VERTEX, {center[0]}, {center[1]}, {center[2]},\n')
axis = ellipse.axes[i] + center
fh.write(f'VERTEX, {axis[0]}, {axis[1]}, {axis[2]},\n')
fh.write("END\n] \n")
fh.write(f"cmd.load_cgo(obj{ellipse_idx},'axis{ellipse_idx}')\n")
fh.write(f"obj{ellipse_idx} = [\n BEGIN, POINTS, \n COLOR, 1.0, 1.0, 0, \n")
#write points
for point in ellipse.points:
fh.write(f'VERTEX, {point[0]}, {point[1]}, {point[2]},\n')
fh.write("END\n ] \n")
fh.write(f"cmd.load_cgo(obj{ellipse_idx},'points{ellipse_idx}'), \n")
full_py_path = os.getcwd() + os.path.sep + py_script
print(f'Pymol script {full_py_path}')
def find_ellipses(programInput: ProgramInput):
mol = None
if '\n' in programInput.smiles:
mol = Chem.MolFromMolBlock(programInput.smiles)
else:
mol = Chem.MolFromSmiles(programInput.smiles)
mol = generate_3d_conformation(mol)
ellipsoids = []
mol = Chem.RemoveAllHs(mol);
if programInput.fragment == True:
ringFinder = RingFinder(mol, programInput.numberNeighbors, programInput.mergeLength)
rings = ringFinder.rings
branches = ringFinder.branches
fragments = list(rings)
fragments.extend(branches)
for fragment in fragments:
# find points on ellipsoid
points = molecule_points(mol, programInput.expandAtom, fragment)
# find MVEE
# Quadratic form defined by square symmetric matrix A and centered at centroid
if len(points) > 1:
A, center = mvee(points);
ellipsoid = quadratic_to_parametric(center, A)
ellipsoid.points = points
ellipsoid.atom_idxs = fragment
ellipsoids.append(ellipsoid)
else:
# find points on ellipsoid
points = molecule_points(mol, programInput.expandAtom)
# find MVEE
# Quadratic form defined by square symmetric matrix A and centered at centroid
A, center = mvee(points);
ellipsoid = quadratic_to_parametric(center, A)
ellipsoid.points = points
ellipsoids.append(ellipsoid)
output = MoleculeOutput(mol, ellipsoids)
return output
if __name__ == '__main__':
parser = argparse.ArgumentParser()
parser.add_argument("--smiles")
parser.add_argument("--expandAtom", action=argparse.BooleanOptionalAction)
parser.add_argument("--fragment", action=argparse.BooleanOptionalAction)
parser.add_argument("--numberNeighbors", nargs='?', const=1, type=int)
parser.add_argument("--mergeLength", nargs='?', const=1, type=int)
args = parser.parse_args()
print(f'Smiles from arguments is {args.smiles}')
print(f'expandAtom from arguments is {args.expandAtom}')
smiles = args.smiles
if not smiles:
print('Using default smiles')
smiles = 'Cc1c(cc([nH]1)C(=O)NC2CCN(CC2)c3ccc4ccccc4n3)Br'
smiles = 'CC(C)C[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CS)C(=O)O'
# In the smiles a period is used to separate multiple molecules- so this smiles is 4 organic compounds and a bunch of salts
# We can only deal with single molecules, so I've selected the first
# smiles = 'CCCCC(=O)N(CC1=CC=C(C=C1)C2=CC=CC=C2C3=NN=N[N-]3)C(C(C)C)C(=O)[O-].CCCCC(=O)N(CC1=CC=C(C=C1)C2=CC=CC=C2C3=NN=N[N-]3)C(C(C)C)C(=O)[O-].CCOC(=O)C(C)CC(CC1=CC=C(C=C1)C2=CC=CC=C2)NC(=O)CCC(=O)[O-].CCOC(=O)C(C)CC(CC1=CC=C(C=C1)C2=CC=CC=C2)NC(=O)CCC(=O)[O-].O.O.O.O.O.[Na+].[Na+].[Na+].[Na+].[Na+].[Na+]'
# smiles = 'CCCCC(=O)N(CC1=CC=C(C=C1)C2=CC=CC=C2C3=NN=N[N-]3)C(C(C)C)C(=O)[O-]'
expandAtom = args.expandAtom
fragment = args.fragment
numberNeighbors = args.numberNeighbors
mergeLength = args.mergeLength
programInput = ProgramInput( expandAtom, smiles, fragment, numberNeighbors, mergeLength)
output = find_ellipses(programInput)
print_pymol_ellipse(output, 'out')