Chimie Théorique » scripts_chimie4psmn » DockOnSurf

"""

Module for generating rdkit molobj/smiles/molecular graph from free atoms

Implementation by Jan H. Jensen, based on the paper

    Yeonjoon Kim and Woo Youn Kim

    "Universal Structure Conversion Method for Organic Molecules: From Atomic Connectivity

    to Three-Dimensional Geometry"

    Bull. Korean Chem. Soc. 2015, Vol. 36, 1769-1777

    DOI: 10.1002/bkcs.10334

"""

import copy

import itertools

from rdkit.Chem import rdmolops

try:

    from rdkit.Chem import rdEHTTools #requires RDKit 2019.9.1 or later

except ImportError:

    rdEHTTools = None

from collections import defaultdict

import numpy as np

import networkx as nx

from rdkit import Chem

from rdkit.Chem import AllChem, rdmolops

global __ATOM_LIST__

__ATOM_LIST__ = \

    ['h',  'he',

     'li', 'be', 'b',  'c',  'n',  'o',  'f',  'ne',

     'na', 'mg', 'al', 'si', 'p',  's',  'cl', 'ar',

     'k',  'ca', 'sc', 'ti', 'v ', 'cr', 'mn', 'fe', 'co', 'ni', 'cu',

     'zn', 'ga', 'ge', 'as', 'se', 'br', 'kr',

     'rb', 'sr', 'y',  'zr', 'nb', 'mo', 'tc', 'ru', 'rh', 'pd', 'ag',

     'cd', 'in', 'sn', 'sb', 'te', 'i',  'xe',

     'cs', 'ba', 'la', 'ce', 'pr', 'nd', 'pm', 'sm', 'eu', 'gd', 'tb', 'dy',

     'ho', 'er', 'tm', 'yb', 'lu', 'hf', 'ta', 'w',  're', 'os', 'ir', 'pt',

     'au', 'hg', 'tl', 'pb', 'bi', 'po', 'at', 'rn',

     'fr', 'ra', 'ac', 'th', 'pa', 'u',  'np', 'pu']

global atomic_valence

global atomic_valence_electrons

atomic_valence = defaultdict(list)

atomic_valence[1] = [1]

atomic_valence[6] = [4]

atomic_valence[7] = [3,4]

atomic_valence[8] = [2,1]

atomic_valence[9] = [1]

atomic_valence[14] = [4]

atomic_valence[15] = [5,3] #[5,4,3]

atomic_valence[16] = [6,3,2] #[6,4,2]

atomic_valence[17] = [1]

atomic_valence[32] = [4]

atomic_valence[35] = [1]

atomic_valence[53] = [1]

atomic_valence_electrons = {}

atomic_valence_electrons[1] = 1

atomic_valence_electrons[6] = 4

atomic_valence_electrons[7] = 5

atomic_valence_electrons[8] = 6

atomic_valence_electrons[9] = 7

atomic_valence_electrons[14] = 4

atomic_valence_electrons[15] = 5

atomic_valence_electrons[16] = 6

atomic_valence_electrons[17] = 7

atomic_valence_electrons[32] = 4

atomic_valence_electrons[35] = 7

atomic_valence_electrons[53] = 7

def str_atom(atom):

    """

    convert integer atom to string atom

    """

    global __ATOM_LIST__

    atom = __ATOM_LIST__[atom - 1]

    return atom

def int_atom(atom):

    """

    convert str atom to integer atom

    """

    global __ATOM_LIST__

    # print(atom)

    atom = atom.lower()

    return __ATOM_LIST__.index(atom) + 1

def get_UA(maxValence_list, valence_list):

    """

    """

    UA = []

    DU = []

    for i, (maxValence, valence) in enumerate(zip(maxValence_list, valence_list)):

        if not maxValence - valence > 0:

            continue

        UA.append(i)

        DU.append(maxValence - valence)

    return UA, DU

def get_BO(AC, UA, DU, valences, UA_pairs, use_graph=True):

    """

    """

    BO = AC.copy()

    DU_save = []

    while DU_save != DU:

        for i, j in UA_pairs:

            BO[i, j] += 1

            BO[j, i] += 1

        BO_valence = list(BO.sum(axis=1))

        DU_save = copy.copy(DU)

        UA, DU = get_UA(valences, BO_valence)

        UA_pairs = get_UA_pairs(UA, AC, use_graph=use_graph)[0]

    return BO

def valences_not_too_large(BO, valences):

    """

    """

    number_of_bonds_list = BO.sum(axis=1)

    for valence, number_of_bonds in zip(valences, number_of_bonds_list):

        if number_of_bonds > valence:

            return False

    return True

def BO_is_OK(BO, AC, charge, DU, atomic_valence_electrons, atoms, valances,

    allow_charged_fragments=True):

    """

    Sanity of bond-orders

    args:

        BO -

        AC -

        charge -

        DU - 

    optional

        allow_charges_fragments - 

    returns:

        boolean - true of molecule is OK, false if not

    """

    if not valences_not_too_large(BO, valances):

        return False

    # total charge

    Q = 0

    # charge fragment list

    q_list = []

    if allow_charged_fragments:

        BO_valences = list(BO.sum(axis=1))

        for i, atom in enumerate(atoms):

            q = get_atomic_charge(atom, atomic_valence_electrons[atom], BO_valences[i])

            Q += q

            if atom == 6:

                number_of_single_bonds_to_C = list(BO[i, :]).count(1)

                if number_of_single_bonds_to_C == 2 and BO_valences[i] == 2:

                    Q += 1

                    q = 2

                if number_of_single_bonds_to_C == 3 and Q + 1 < charge:

                    Q += 2

                    q = 1

            if q != 0:

                q_list.append(q)

    check_sum = (BO - AC).sum() == sum(DU)

    check_charge = charge == Q

    # check_len = len(q_list) <= abs(charge)

    if check_sum and check_charge:

        return True

    return False

def get_atomic_charge(atom, atomic_valence_electrons, BO_valence):

    """

    """

    if atom == 1:

        charge = 1 - BO_valence

    elif atom == 5:

        charge = 3 - BO_valence

    elif atom == 15 and BO_valence == 5:

        charge = 0

    elif atom == 16 and BO_valence == 6:

        charge = 0

    else:

        charge = atomic_valence_electrons - 8 + BO_valence

    return charge

def clean_charges(mol):

    """

    This hack should not be needed anymore, but is kept just in case

    """

    Chem.SanitizeMol(mol)

    #rxn_smarts = ['[N+:1]=[*:2]-[C-:3]>>[N+0:1]-[*:2]=[C-0:3]',

    #              '[N+:1]=[*:2]-[O-:3]>>[N+0:1]-[*:2]=[O-0:3]',

    #              '[N+:1]=[*:2]-[*:3]=[*:4]-[O-:5]>>[N+0:1]-[*:2]=[*:3]-[*:4]=[O-0:5]',

    #              '[#8:1]=[#6:2]([!-:6])[*:3]=[*:4][#6-:5]>>[*-:1][*:2]([*:6])=[*:3][*:4]=[*+0:5]',

    #              '[O:1]=[c:2][c-:3]>>[*-:1][*:2][*+0:3]',

    #              '[O:1]=[C:2][C-:3]>>[*-:1][*:2]=[*+0:3]']

    rxn_smarts = ['[#6,#7:1]1=[#6,#7:2][#6,#7:3]=[#6,#7:4][CX3-,NX3-:5][#6,#7:6]1=[#6,#7:7]>>'

                  '[#6,#7:1]1=[#6,#7:2][#6,#7:3]=[#6,#7:4][-0,-0:5]=[#6,#7:6]1[#6-,#7-:7]',

                  '[#6,#7:1]1=[#6,#7:2][#6,#7:3](=[#6,#7:4])[#6,#7:5]=[#6,#7:6][CX3-,NX3-:7]1>>'

                  '[#6,#7:1]1=[#6,#7:2][#6,#7:3]([#6-,#7-:4])=[#6,#7:5][#6,#7:6]=[-0,-0:7]1']

    fragments = Chem.GetMolFrags(mol,asMols=True,sanitizeFrags=False)

    for i, fragment in enumerate(fragments):

        for smarts in rxn_smarts:

            patt = Chem.MolFromSmarts(smarts.split(">>")[0])

            while fragment.HasSubstructMatch(patt):

                rxn = AllChem.ReactionFromSmarts(smarts)

                ps = rxn.RunReactants((fragment,))

                fragment = ps[0][0]

                Chem.SanitizeMol(fragment)

        if i == 0:

            mol = fragment

        else:

            mol = Chem.CombineMols(mol, fragment)

    return mol

def BO2mol(mol, BO_matrix, atoms, atomic_valence_electrons,

           mol_charge, allow_charged_fragments=True):

    """

    based on code written by Paolo Toscani

    From bond order, atoms, valence structure and total charge, generate an

    rdkit molecule.

    args:

        mol - rdkit molecule

        BO_matrix - bond order matrix of molecule

        atoms - list of integer atomic symbols

        atomic_valence_electrons -

        mol_charge - total charge of molecule

    optional:

        allow_charged_fragments - bool - allow charged fragments

    returns

        mol - updated rdkit molecule with bond connectivity

    """

    l = len(BO_matrix)

    l2 = len(atoms)

    BO_valences = list(BO_matrix.sum(axis=1))

    if (l != l2):

        raise RuntimeError('sizes of adjMat ({0:d}) and Atoms {1:d} differ'.format(l, l2))

    rwMol = Chem.RWMol(mol)

    bondTypeDict = {

        1: Chem.BondType.SINGLE,

        2: Chem.BondType.DOUBLE,

        3: Chem.BondType.TRIPLE

    }

    for i in range(l):

        for j in range(i + 1, l):

            bo = int(round(BO_matrix[i, j]))

            if (bo == 0):

                continue

            bt = bondTypeDict.get(bo, Chem.BondType.SINGLE)

            rwMol.AddBond(i, j, bt)

    mol = rwMol.GetMol()

    if allow_charged_fragments:

        mol = set_atomic_charges(

            mol,

            atoms,

            atomic_valence_electrons,

            BO_valences,

            BO_matrix,

            mol_charge)

    else:

        mol = set_atomic_radicals(mol, atoms, atomic_valence_electrons, BO_valences)

    return mol

def set_atomic_charges(mol, atoms, atomic_valence_electrons,

                       BO_valences, BO_matrix, mol_charge):

    """

    """

    q = 0

    for i, atom in enumerate(atoms):

        a = mol.GetAtomWithIdx(i)

        charge = get_atomic_charge(atom, atomic_valence_electrons[atom], BO_valences[i])

        q += charge

        if atom == 6:

            number_of_single_bonds_to_C = list(BO_matrix[i, :]).count(1)

            if number_of_single_bonds_to_C == 2 and BO_valences[i] == 2:

                q += 1

                charge = 0

            if number_of_single_bonds_to_C == 3 and q + 1 < mol_charge:

                q += 2

                charge = 1

        if (abs(charge) > 0):

            a.SetFormalCharge(int(charge))

    mol = clean_charges(mol)

    return mol

def set_atomic_radicals(mol, atoms, atomic_valence_electrons, BO_valences):

    """

    The number of radical electrons = absolute atomic charge

    """

    for i, atom in enumerate(atoms):

        a = mol.GetAtomWithIdx(i)

        charge = get_atomic_charge(

            atom,

            atomic_valence_electrons[atom],

            BO_valences[i])

        if (abs(charge) > 0):

            a.SetNumRadicalElectrons(abs(int(charge)))

    return mol

def get_bonds(UA, AC):

    """

    """

    bonds = []

    for k, i in enumerate(UA):

        for j in UA[k + 1:]:

            if AC[i, j] == 1:

                bonds.append(tuple(sorted([i, j])))

    return bonds

def get_UA_pairs(UA, AC, use_graph=True):

    """

    """

    bonds = get_bonds(UA, AC)

    if len(bonds) == 0:

        return [()]

    if use_graph:

        G = nx.Graph()

        G.add_edges_from(bonds)

        UA_pairs = [list(nx.max_weight_matching(G))]

        return UA_pairs

    max_atoms_in_combo = 0

    UA_pairs = [()]

    for combo in list(itertools.combinations(bonds, int(len(UA) / 2))):

        flat_list = [item for sublist in combo for item in sublist]

        atoms_in_combo = len(set(flat_list))

        if atoms_in_combo > max_atoms_in_combo:

            max_atoms_in_combo = atoms_in_combo

            UA_pairs = [combo]

        elif atoms_in_combo == max_atoms_in_combo:

            UA_pairs.append(combo)

    return UA_pairs

def AC2BO(AC, atoms, charge, allow_charged_fragments=True, use_graph=True):

    """

    implemenation of algorithm shown in Figure 2

    UA: unsaturated atoms

    DU: degree of unsaturation (u matrix in Figure)

    best_BO: Bcurr in Figure

    """

    global atomic_valence

    global atomic_valence_electrons

    # make a list of valences, e.g. for CO: [[4],[2,1]]

    valences_list_of_lists = []

    AC_valence = list(AC.sum(axis=1))

    for atomicNum in atoms:

        valences_list_of_lists.append(atomic_valence[atomicNum])

    # convert [[4],[2,1]] to [[4,2],[4,1]]

    valences_list = itertools.product(*valences_list_of_lists)

    best_BO = AC.copy()

    for valences in valences_list:

        UA, DU_from_AC = get_UA(valences, AC_valence)

        check_len = (len(UA) == 0)

        if check_len:

            check_bo = BO_is_OK(AC, AC, charge, DU_from_AC,

                atomic_valence_electrons, atoms, valences,

                allow_charged_fragments=allow_charged_fragments)

        else:

            check_bo = None

        if check_len and check_bo:

            return AC, atomic_valence_electrons

        UA_pairs_list = get_UA_pairs(UA, AC, use_graph=use_graph)

        for UA_pairs in UA_pairs_list:

            BO = get_BO(AC, UA, DU_from_AC, valences, UA_pairs, use_graph=use_graph)

            status = BO_is_OK(BO, AC, charge, DU_from_AC,

                        atomic_valence_electrons, atoms, valences,

                        allow_charged_fragments=allow_charged_fragments)

            if status:

                return BO, atomic_valence_electrons

            elif BO.sum() >= best_BO.sum() and valences_not_too_large(BO, valences):

                best_BO = BO.copy()

    return best_BO, atomic_valence_electrons

def AC2mol(mol, AC, atoms, charge, allow_charged_fragments=True, use_graph=True):

    """

    """

    # convert AC matrix to bond order (BO) matrix

    BO, atomic_valence_electrons = AC2BO(

        AC,

        atoms,

        charge,

        allow_charged_fragments=allow_charged_fragments,

        use_graph=use_graph)

    # add BO connectivity and charge info to mol object

    mol = BO2mol(

        mol,

        BO,

        atoms,

        atomic_valence_electrons,

        charge,

        allow_charged_fragments=allow_charged_fragments)

    return mol

def get_proto_mol(atoms):

    """

    """

    mol = Chem.MolFromSmarts("[#" + str(atoms[0]) + "]")

    rwMol = Chem.RWMol(mol)

    for i in range(1, len(atoms)):

        a = Chem.Atom(atoms[i])

        rwMol.AddAtom(a)

    mol = rwMol.GetMol()

    return mol

def read_xyz_file(filename, look_for_charge=True):

    """

    """

    atomic_symbols = []

    xyz_coordinates = []

    charge = 0

    title = ""

    with open(filename, "r") as file:

        for line_number, line in enumerate(file):

            if line_number == 0:

                num_atoms = int(line)

            elif line_number == 1:

                title = line

                if "charge=" in line:  # TODO: More flexible charge declaration

                    charge = int(line.split("=")[1])

            else:

                atomic_symbol, x, y, z = line.split()

                atomic_symbols.append(atomic_symbol)

                xyz_coordinates.append([float(x), float(y), float(z)])

    atoms = [int_atom(atom) for atom in atomic_symbols]

    return atoms, charge, xyz_coordinates

def xyz2AC(atoms, xyz, charge, use_huckel=False):

    """

    atoms and coordinates to atom connectivity (AC)

    args:

        atoms - int atom types

        xyz - coordinates

        charge - molecule charge

    optional:

        use_huckel - Use Huckel method for atom connecitivty

    returns

        ac - atom connectivity matrix

        mol - rdkit molecule

    """

    if use_huckel:

        return xyz2AC_huckel(atoms, xyz, charge)

    else:

        return xyz2AC_vdW(atoms, xyz)

def xyz2AC_vdW(atoms, xyz):

    # Get mol template

    mol = get_proto_mol(atoms)

    # Set coordinates

    conf = Chem.Conformer(mol.GetNumAtoms())

    for i in range(mol.GetNumAtoms()):

        conf.SetAtomPosition(i, (xyz[i][0], xyz[i][1], xyz[i][2]))

    mol.AddConformer(conf)

    AC = get_AC(mol)

    return AC, mol

def get_AC(mol, covalent_factor=1.3):

    """

    Generate adjacent matrix from atoms and coordinates.

    AC is a (num_atoms, num_atoms) matrix with 1 being covalent bond and 0 is not

    covalent_factor - 1.3 is an arbitrary factor

    args:

        mol - rdkit molobj with 3D conformer

    optional

        covalent_factor - increase covalent bond length threshold with facto

    returns:

        AC - adjacent matrix

    """

    # Calculate distance matrix

    dMat = Chem.Get3DDistanceMatrix(mol)

    pt = Chem.GetPeriodicTable()

    num_atoms = mol.GetNumAtoms()

    AC = np.zeros((num_atoms, num_atoms), dtype=int)

    for i in range(num_atoms):

        a_i = mol.GetAtomWithIdx(i)

        Rcov_i = pt.GetRcovalent(a_i.GetAtomicNum()) * covalent_factor

        for j in range(i + 1, num_atoms):

            a_j = mol.GetAtomWithIdx(j)

            Rcov_j = pt.GetRcovalent(a_j.GetAtomicNum()) * covalent_factor

            if dMat[i, j] <= Rcov_i + Rcov_j:

                AC[i, j] = 1

                AC[j, i] = 1

    return AC

def xyz2AC_huckel(atomicNumList,xyz,charge):

    """

    args

        atomicNumList - atom type list

        xyz - coordinates

        charge - molecule charge

    returns

        ac - atom connectivity

        mol - rdkit molecule

    """

    mol = get_proto_mol(atomicNumList)

    conf = Chem.Conformer(mol.GetNumAtoms())

    for i in range(mol.GetNumAtoms()):

        conf.SetAtomPosition(i,(xyz[i][0],xyz[i][1],xyz[i][2]))

    mol.AddConformer(conf)

    num_atoms = len(atomicNumList)

    AC = np.zeros((num_atoms,num_atoms)).astype(int)

    mol_huckel = Chem.Mol(mol)

    mol_huckel.GetAtomWithIdx(0).SetFormalCharge(charge) #mol charge arbitrarily added to 1st atom    

    passed,result = rdEHTTools.RunMol(mol_huckel)

    opop = result.GetReducedOverlapPopulationMatrix()

    tri = np.zeros((num_atoms, num_atoms))

    tri[np.tril(np.ones((num_atoms, num_atoms), dtype=bool))] = opop #lower triangular to square matrix

    for i in range(num_atoms):

        for j in range(i+1,num_atoms):

            pair_pop = abs(tri[j,i])   

            if pair_pop >= 0.15: #arbitry cutoff for bond. May need adjustment

                AC[i,j] = 1

                AC[j,i] = 1

    return AC, mol

def chiral_stereo_check(mol):

    """

    Find and embed chiral information into the model based on the coordinates

    args:

        mol - rdkit molecule, with embeded conformer

    """

    Chem.SanitizeMol(mol)

    Chem.DetectBondStereochemistry(mol, -1)

    Chem.AssignStereochemistry(mol, flagPossibleStereoCenters=True, force=True)

    Chem.AssignAtomChiralTagsFromStructure(mol, -1)

    return

def xyz2mol(atoms, coordinates,

    charge=0,

    allow_charged_fragments=True,

    use_graph=True,

    use_huckel=False,

    embed_chiral=True):

    """

    Generate a rdkit molobj from atoms, coordinates and a total_charge.

    args:

        atoms - list of atom types (int)

        coordinates - 3xN Cartesian coordinates

        charge - total charge of the system (default: 0)

    optional:

        allow_charged_fragments - alternatively radicals are made

        use_graph - use graph (networkx)

        use_huckel - Use Huckel method for atom connectivity prediction

        embed_chiral - embed chiral information to the molecule

    returns:

        mol - rdkit molobj

    """

    # Get atom connectivity (AC) matrix, list of atomic numbers, molecular charge,

    # and mol object with no connectivity information

    # print("atoms variable: ", atoms)

    AC, mol = xyz2AC(atoms, coordinates, charge, use_huckel=use_huckel)

    # Convert AC to bond order matrix and add connectivity and charge info to

    # mol object

    new_mol = AC2mol(mol, AC, atoms, charge,

        allow_charged_fragments=allow_charged_fragments,

        use_graph=use_graph)

    # Check for stereocenters and chiral centers

    if embed_chiral:

        chiral_stereo_check(new_mol)

    return new_mol

def main():

    return

if __name__ == "__main__":

    import argparse

    parser = argparse.ArgumentParser() # usage='%(prog)s [options] molecule.xyz')

    parser.add_argument('structure', metavar='structure', type=str)

    parser.add_argument('-s', '--sdf',

        action="store_true",

        help="Dump sdf file")

    parser.add_argument('--ignore-chiral',

        action="store_true",

        help="Ignore chiral centers")

    parser.add_argument('--no-charged-fragments',

        action="store_true",

        help="Allow radicals to be made")

    parser.add_argument('--no-graph',

        action="store_true",

        help="Run xyz2mol without networkx dependencies")

    # huckel uses extended Huckel bond orders to locate bonds (requires RDKit 2019.9.1 or later)

    # otherwise van der Waals radii are used

    parser.add_argument('--use-huckel',

        action="store_true",

        help="Use Huckel method for atom connectivity")

    parser.add_argument('-o', '--output-format',

        action="store",

        type=str,

        help="Output format [smiles,sdf] (default=sdf)")

    parser.add_argument('-c', '--charge',

        action="store",

        metavar="int",

        type=int,

        help="Total charge of the system")

    args = parser.parse_args()

    # read xyz file

    filename = args.structure

    # allow for charged fragments, alternatively radicals are made

    charged_fragments = not args.no_charged_fragments

    # quick is faster for large systems but requires networkx

    # if you don't want to install networkx set quick=False and

    # uncomment 'import networkx as nx' at the top of the file

    quick = not args.no_graph

    # chiral comment

    embed_chiral = not args.ignore_chiral

    # read atoms and coordinates. Try to find the charge

    atoms, charge, xyz_coordinates = read_xyz_file(filename)

    # huckel uses extended Huckel bond orders to locate bonds (requires RDKit 2019.9.1 or later)

    # otherwise van der Waals radii are used

    use_huckel = args.use_huckel

    # if explicit charge from args, set it

    if args.charge is not None:

        charge = int(args.charge)

    # Get the molobj

    mol = xyz2mol(atoms, xyz_coordinates,

        charge=charge,

        use_graph=quick,

        allow_charged_fragments=charged_fragments,

        embed_chiral=embed_chiral,

        use_huckel=use_huckel)