import copy import json import math import numpy as np import pandas as pd import torch from scipy.spatial import cKDTree from rdkit import Chem from rdkit.Chem import RWMol from rdkit.Chem import Draw, AllChem from rdkit.Chem import rdDepictor import matplotlib.pyplot as plt import re def output_to_smiles(output,idx_to_labels,bond_labels,result): x_center = (output["boxes"][:, 0] + output["boxes"][:, 2]) / 2 y_center = (output["boxes"][:, 1] + output["boxes"][:, 3]) / 2 center_coords = torch.stack((x_center, y_center), dim=1) output = {'bbox': output["boxes"].to("cpu").numpy(), 'bbox_centers': center_coords.to("cpu").numpy(), 'scores': output["scores"].to("cpu").numpy(), 'pred_classes': output["labels"].to("cpu").numpy()} atoms_list, bonds_list = bbox_to_graph_with_charge(output, idx_to_labels=idx_to_labels, bond_labels=bond_labels, result=result) #NOTE print return mol_from_graph_with_chiral(atoms_list, bonds_list) def bbox_to_graph(output, idx_to_labels, bond_labels,result): # calculate atoms mask (pred classes that are atoms/bonds) atoms_mask = np.array([True if ins not in bond_labels else False for ins in output['pred_classes']]) # get atom list atoms_list = [idx_to_labels[a] for a in output['pred_classes'][atoms_mask]] # if len(result) !=0 and 'other' in atoms_list: # new_list = [] # replace_index = 0 # for item in atoms_list: # if item == 'other': # new_list.append(result[replace_index % len(result)]) # replace_index += 1 # else: # new_list.append(item) # atoms_list = new_list atoms_list = pd.DataFrame({'atom': atoms_list, 'x': output['bbox_centers'][atoms_mask, 0], 'y': output['bbox_centers'][atoms_mask, 1]}) # in case atoms with sign gets detected two times, keep only the signed one for idx, row in atoms_list.iterrows(): if row.atom[-1] != '0': if row.atom[-2] != '-':#assume charge value -9~9 overlapping = atoms_list[atoms_list.atom.str.startswith(row.atom[:-1])] else: overlapping = atoms_list[atoms_list.atom.str.startswith(row.atom[:-2])] kdt = cKDTree(overlapping[['x', 'y']]) dists, neighbours = kdt.query([row.x, row.y], k=2) if dists[1] < 7: atoms_list.drop(overlapping.index[neighbours[1]], axis=0, inplace=True) bonds_list = [] # get bonds for bbox, bond_type, score in zip(output['bbox'][np.logical_not(atoms_mask)], output['pred_classes'][np.logical_not(atoms_mask)], output['scores'][np.logical_not(atoms_mask)]): # if idx_to_labels[bond_type] == 'SINGLE': if idx_to_labels[bond_type] in ['-','SINGLE', 'NONE', 'ENDUPRIGHT', 'BEGINWEDGE', 'BEGINDASH', 'ENDDOWNRIGHT']: _margin = 5 else: _margin = 8 # anchor positions are _margin distances away from the corners of the bbox. anchor_positions = (bbox + [_margin, _margin, -_margin, -_margin]).reshape([2, -1]) oposite_anchor_positions = anchor_positions.copy() oposite_anchor_positions[:, 1] = oposite_anchor_positions[:, 1][::-1] # Upper left, lower right, lower left, upper right # 0 - 1, 2 - 3 anchor_positions = np.concatenate([anchor_positions, oposite_anchor_positions]) # get the closest point to every corner atoms_pos = atoms_list[['x', 'y']].values kdt = cKDTree(atoms_pos) dists, neighbours = kdt.query(anchor_positions, k=1) # check corner with the smallest total distance to closest atoms if np.argmin((dists[0] + dists[1], dists[2] + dists[3])) == 0: # visualize setup begin_idx, end_idx = neighbours[:2] else: # visualize setup begin_idx, end_idx = neighbours[2:] #NOTE this proces may lead self-bonding for one atom if begin_idx != end_idx:# avoid self-bond bonds_list.append((begin_idx, end_idx, idx_to_labels[bond_type], idx_to_labels[bond_type], score)) else: continue # return atoms_list.atom.values.tolist(), bonds_list return atoms_list, bonds_list def calculate_distance(coord1, coord2): # Calculate Euclidean distance between two coordinates return math.sqrt((coord1[0] - coord2[0])**2 + (coord1[1] - coord2[1])**2) def assemble_atoms_with_charges(atom_list, charge_list): used_charge_indices=set() atom_list['atom'] = atom_list['atom'] + '0' kdt = cKDTree(atom_list[['x','y']]) for i, charge in charge_list.iterrows(): if i in used_charge_indices: continue charge_=charge['charge'] if charge_=='1':charge_='+' dist, idx_atom=kdt.query([charge_list.x[i],charge_list.y[i]], k=1) atom_str=atom_list.loc[idx_atom,'atom'] atom_ = re.findall(r'[A-Za-z]+', atom_str)[0] + charge_ atom_list.loc[idx_atom,'atom']=atom_ return atom_list def assemble_atoms_with_charges2(atom_list, charge_list, max_distance=10): used_charge_indices = set() for idx, atom in atom_list.iterrows(): atom_coord = atom['x'],atom['y'] atom_label = atom['atom'] closest_charge = None min_distance = float('inf') for i, charge in charge_list.iterrows(): if i in used_charge_indices: continue charge_coord = charge['x'],charge['y'] charge_label = charge['charge'] distance = calculate_distance(atom_coord, charge_coord) #NOTE how t determin this max_distance, dependent on image size?? if distance <= max_distance and distance < min_distance: closest_charge = charge min_distance = distance if closest_charge is not None: if closest_charge['charge'] == '1': charge_ = '+' else: charge_ = closest_charge['charge'] atom_ = atom['atom'] + charge_ # atom['atom'] = atom_ atom_list.loc[idx,'atom'] = atom_ used_charge_indices.add(tuple(charge)) else: # atom['atom'] = atom['atom'] + '0' atom_list.loc[idx,'atom'] = atom['atom'] + '0' return atom_list def bbox_to_graph_with_charge(output, idx_to_labels, bond_labels,result): bond_labels_pre=bond_labels charge_labels = [18,19,20,21,22]#make influence atoms_mask = np.array([True if ins not in bond_labels and ins not in charge_labels else False for ins in output['pred_classes']]) atoms_list = [idx_to_labels[a] for a in output['pred_classes'][atoms_mask]] atoms_list = pd.DataFrame({'atom': atoms_list, 'x': output['bbox_centers'][atoms_mask, 0], 'y': output['bbox_centers'][atoms_mask, 1], 'bbox': output['bbox'][atoms_mask].tolist() ,#need this for */other converting }) charge_mask = np.array([True if ins in charge_labels else False for ins in output['pred_classes']]) charge_list = [idx_to_labels[a] for a in output['pred_classes'][charge_mask]] charge_list = pd.DataFrame({'charge': charge_list, 'x': output['bbox_centers'][charge_mask, 0], 'y': output['bbox_centers'][charge_mask, 1]}) # print(charge_list,'\n@bbox_to_graph_with_charge') if len(charge_list) > 0: atoms_list = assemble_atoms_with_charges(atoms_list,charge_list) else:#Note Most mols are not formal charged atoms_list['atom'] = atoms_list['atom']+'0' # print(atoms_list,"after @@assemble_atoms_with_charges ") # in case atoms with sign gets detected two times, keep only the signed one for idx, row in atoms_list.iterrows(): if row.atom[-1] != '0': try: if row.atom[-2] != '-':#assume charge value -9~9 overlapping = atoms_list[atoms_list.atom.str.startswith(row.atom[:-1])] except Exception as e: print(row.atom,"@row.atom") print(e) else: overlapping = atoms_list[atoms_list.atom.str.startswith(row.atom[:-2])] kdt = cKDTree(overlapping[['x', 'y']]) dists, neighbours = kdt.query([row.x, row.y], k=2) if dists[1] < 7: atoms_list.drop(overlapping.index[neighbours[1]], axis=0, inplace=True) bonds_list = [] # get bonds # bond_mask=np.logical_not(np.logical_not(atoms_mask) | np.logical_not(charge_mask)) bond_mask=np.logical_not(atoms_mask) & np.logical_not(charge_mask) for bbox, bond_type, score in zip(output['bbox'][bond_mask], #NOTE also including the charge part output['pred_classes'][bond_mask], output['scores'][bond_mask]): # if idx_to_labels[bond_type] == 'SINGLE': if idx_to_labels[bond_type] in ['-','SINGLE', 'NONE', 'ENDUPRIGHT', 'BEGINWEDGE', 'BEGINDASH', 'ENDDOWNRIGHT']: _margin = 5 else: _margin = 8 # anchor positions are _margin distances away from the corners of the bbox. anchor_positions = (bbox + [_margin, _margin, -_margin, -_margin]).reshape([2, -1]) oposite_anchor_positions = anchor_positions.copy() oposite_anchor_positions[:, 1] = oposite_anchor_positions[:, 1][::-1] # Upper left, lower right, lower left, upper right # 0 - 1, 2 - 3 anchor_positions = np.concatenate([anchor_positions, oposite_anchor_positions]) # get the closest point to every corner atoms_pos = atoms_list[['x', 'y']].values kdt = cKDTree(atoms_pos) dists, neighbours = kdt.query(anchor_positions, k=1) # check corner with the smallest total distance to closest atoms if np.argmin((dists[0] + dists[1], dists[2] + dists[3])) == 0: # visualize setup begin_idx, end_idx = neighbours[:2] else: # visualize setup begin_idx, end_idx = neighbours[2:] #NOTE this proces may lead self-bonding for one atom if begin_idx != end_idx: if bond_type in bond_labels:# avoid self-bond bonds_list.append((begin_idx, end_idx, idx_to_labels[bond_type], idx_to_labels[bond_type], score)) else: print(f'this box may be charges box not bonds {[bbox, bond_type, score ]}') else: continue # return atoms_list.atom.values.tolist(), bonds_list # print(f"@box2graph: atom,bond nums:: {len(atoms_list)}, {len(bonds_list)}") return atoms_list, bonds_list#dataframe, list def mol_from_graph_with_chiral(atoms_list, bonds): mol = RWMol() nodes_idx = {} atoms = atoms_list.atom.values.tolist() coords = [(row['x'], 300-row['y'], 0) for index, row in atoms_list.iterrows()] coords = tuple(coords) coords = tuple(tuple(num / 100 for num in sub_tuple) for sub_tuple in coords) # points = [(row['x'], 300-row['y']) for index, row in atoms_list.iterrows()] # plt.figure(figsize=(6, 6)) # for point in points: # plt.scatter(point[0], point[1], color='blue') # plt.xlim(0, 300) # plt.ylim(300, 0) # plt.gca().set_aspect('equal', adjustable='box') # plt.savefig('/home/jovyan/rt-detr/output/test/plot.png') for i in range(len(bonds)): idx_1, idx_2, bond_type, bond_dir, score = bonds[i] if bond_type in ['-', 'NONE', 'ENDUPRIGHT', 'BEGINWEDGE', 'BEGINDASH', 'ENDDOWNRIGHT']: bonds[i] = (idx_1, idx_2, 'SINGLE', bond_dir, score) elif bond_type == '=': bonds[i] = (idx_1, idx_2, 'DOUBLE', bond_dir, score) elif bond_type == '#': bonds[i] = (idx_1, idx_2, 'TRIPLE', bond_dir, score) bond_types = {'SINGLE': Chem.rdchem.BondType.SINGLE, 'DOUBLE': Chem.rdchem.BondType.DOUBLE, 'TRIPLE': Chem.rdchem.BondType.TRIPLE, 'AROMATIC': Chem.rdchem.BondType.AROMATIC} bond_dirs = {'NONE': Chem.rdchem.BondDir.NONE, 'ENDUPRIGHT': Chem.rdchem.BondDir.ENDUPRIGHT, 'BEGINWEDGE': Chem.rdchem.BondDir.BEGINWEDGE, 'BEGINDASH': Chem.rdchem.BondDir.BEGINDASH, 'ENDDOWNRIGHT': Chem.rdchem.BondDir.ENDDOWNRIGHT,} try: # add nodes s10=[str(x) for x in range(10)] for idx, node in enumerate(atoms):#NOTE no formal charge will be X0 here # node=node.split(' ') # if ('0' in node) or ('1' in node): if 'other' in node: a='*' if '-' in node or '+' in node: fc = int(node[-2:]) else: fc = int(node[-1]) elif node[-1] in s10: if '-' in node or '+' in node: a = node[:-2] fc = int(node[-2:]) else: a = node[:-1] fc = int(node[-1]) elif node[-1]=='+': a = node[:-1] fc = 1 elif node[-1]=='-': a = node[:-1] fc = -1 # elif ('-1' in node) or ('-' in node): # a = node[:-2] # fc = int(node[-2]) else: a = node fc = 0 ad = Chem.Atom(a) ad.SetFormalCharge(fc) atom_idx = mol.AddAtom(ad) nodes_idx[idx] = atom_idx # add bonds existing_bonds = set() for idx_1, idx_2, bond_type, bond_dir, score in bonds: if (idx_1 in nodes_idx) and (idx_2 in nodes_idx): if (idx_1, idx_2) not in existing_bonds and (idx_2, idx_1) not in existing_bonds: try: mol.AddBond(nodes_idx[idx_1], nodes_idx[idx_2], bond_types[bond_type]) except Exception as e: print([idx_1, idx_2, bond_type, bond_dir, score],f"erro @add bonds ") print(f"erro@add existing_bonds: {e}\n{bonds}") continue existing_bonds.add((idx_1, idx_2)) if Chem.MolFromSmiles(Chem.MolToSmiles(mol.GetMol())): prev_mol = copy.deepcopy(mol) else: mol = copy.deepcopy(prev_mol) chiral_centers = Chem.FindMolChiralCenters( mol, includeUnassigned=True, includeCIP=False, useLegacyImplementation=False) chiral_center_ids = [idx for idx, _ in chiral_centers] for id in chiral_center_ids: for index, tup in enumerate(bonds): if id == tup[1]: new_tup = tuple([tup[1], tup[0], tup[2], tup[3], tup[4]])#idx_1, idx_2, bond_type, bond_dir, score bonds[index] = new_tup mol.RemoveBond(int(tup[0]), int(tup[1])) try: mol.AddBond(int(tup[1]), int(tup[0]), bond_types[tup[2]]) except Exception as e: print( index, tup, id) print(f"bonds: {bonds}") print(f"erro@chiral_center_ids: {e}") mol = mol.GetMol() # if 'S0' in atoms: # bonds_ = [[row[0], row[1], row[3]] for row in bonds] # n_atoms=len(atoms) # for i in chiral_center_ids: # for j in range(n_atoms): # if [i,j,'BEGINWEDGE'] in bonds_: # mol.GetBondBetweenAtoms(i, j).SetBondDir(bond_dirs['BEGINWEDGE']) # elif [i,j,'BEGINDASH'] in bonds_: # mol.GetBondBetweenAtoms(i, j).SetBondDir(bond_dirs['BEGINDASH']) # Chem.SanitizeMol(mol) # AllChem.Compute2DCoords(mol) # Chem.AssignChiralTypesFromBondDirs(mol) # Chem.AssignStereochemistry(mol, force=True, cleanIt=True) # else: mol.RemoveAllConformers() conf = Chem.Conformer(mol.GetNumAtoms()) conf.Set3D(True) for i, (x, y, z) in enumerate(coords): conf.SetAtomPosition(i, (x, y, z)) mol.AddConformer(conf) # Chem.SanitizeMol(mol) Chem.AssignStereochemistryFrom3D(mol) bonds_ = [[row[0], row[1], row[3]] for row in bonds] n_atoms=len(atoms) for i in chiral_center_ids: for j in range(n_atoms): if [i,j,'BEGINWEDGE'] in bonds_: mol.GetBondBetweenAtoms(i, j).SetBondDir(bond_dirs['BEGINWEDGE']) elif [i,j,'BEGINDASH'] in bonds_: mol.GetBondBetweenAtoms(i, j).SetBondDir(bond_dirs['BEGINDASH']) Chem.SanitizeMol(mol) Chem.DetectBondStereochemistry(mol) Chem.AssignChiralTypesFromBondDirs(mol) Chem.AssignStereochemistry(mol) # mol.Debug() # print('debuged') # drawing out # opts = Draw.MolDrawOptions() # opts.addAtomIndices = False # opts.addStereoAnnotation = False # img = Draw.MolToImage(mol, options=opts,size=(1000, 1000)) # img.save('tttttttttttttafter.png') # Chem.Draw.MolToImageFile(mol, 'tttttttttttttbefore.png') # img.save('/home/jovyan/rt-detr/output/test/after.png') # Chem.Draw.MolToImageFile(mol, '/home/jovyan/rt-detr/output/test/before.png') smiles=Chem.MolToSmiles(mol) return smiles,mol except Chem.rdchem.AtomValenceException as e: print(f"捕获到 AtomValenceException 异常@@{e}") # except Chem.rdchem.AtomValenceException as e: # print(f"捕获到 AtomValenceException 异常@@{e}") except Exception as e: print(f"捕获到 异常@@{e}") print(f"Error@@node {node} atom@@ {a} \n") print(atoms,idx,atoms[idx]) def mol_from_graph_without_chiral(atoms, bonds): mol = RWMol() nodes_idx = {} for i in range(len(bonds)): idx_1, idx_2, bond_type, bond_dir, score = bonds[i] if bond_type in ['-', 'NONE', 'ENDUPRIGHT', 'BEGINWEDGE', 'BEGINDASH', 'ENDDOWNRIGHT']: bonds[i] = (idx_1, idx_2, 'SINGLE', bond_dir, score) elif bond_type == '=': bonds[i] = (idx_1, idx_2, 'DOUBLE', bond_dir, score) elif bond_type == '#': bonds[i] = (idx_1, idx_2, 'TRIPLE', bond_dir, score) bond_types = {'SINGLE': Chem.rdchem.BondType.SINGLE, 'DOUBLE': Chem.rdchem.BondType.DOUBLE, 'TRIPLE': Chem.rdchem.BondType.TRIPLE, 'AROMATIC': Chem.rdchem.BondType.AROMATIC} try: # add nodes for idx, node in enumerate(atoms): if ('0' in node) or ('1' in node): a = node[:-1] fc = int(node[-1]) if '-1' in node: a = node[:-2] fc = -1 a = Chem.Atom(a) a.SetFormalCharge(fc) atom_idx = mol.AddAtom(a) nodes_idx[idx] = atom_idx # add bonds existing_bonds = set() for idx_1, idx_2, bond_type, bond_dir, score in bonds: if (idx_1 in nodes_idx) and (idx_2 in nodes_idx): if (idx_1, idx_2) not in existing_bonds and (idx_2, idx_1) not in existing_bonds: try: mol.AddBond(nodes_idx[idx_1], nodes_idx[idx_2], bond_types[bond_type]) except: continue existing_bonds.add((idx_1, idx_2)) if Chem.MolFromSmiles(Chem.MolToSmiles(mol.GetMol())): prev_mol = copy.deepcopy(mol) else: mol = copy.deepcopy(prev_mol) mol = mol.GetMol() mol = Chem.MolFromSmiles(Chem.MolToSmiles(mol)) return Chem.MolToSmiles(mol) except Chem.rdchem.AtomValenceException as e: print("捕获到 AtomValenceException 异常")