Representation of Molecules can be done in the form of graphs. To existing generative models on graph data structures, we need better algorithms. Junction Tree VAE helps to address this issue and creates better molecular graphs.

Brief introduction

Molecular structure generation is one of the major parts of a material or drug discovery. This task involves continuous embedding and generation of molecular graphs. Our junction tree variational autoencoder generates molecular graphs in two phases:
(i)First, generating a tree-structured scaffold over chemical substructures
. (ii)Combining them into a molecule with a graph message-passing network.


A molecular graph G is first decomposed into its junction tree TG, where each coloured node in the tree represents a substructure in the molecule.We then encode both the tree and graph into their latent embeddings zT and zG. To decode the molecule, we first reconstruct junction tree from zT , and then assemble nodes in the tree back to the original molecule.


I’ll be showing you how I built my Junction tree VAE in Pytorch. The dataset I used is ZINC dataset.The dataset contains smiles representation of molecules.I have also used RDKit to process the molecules.

I.Data Preprocessing

(i)Import the text file into our code.

with open('train.txt') as f:
    data = [line.strip("\r\n ").split()[0] for line in f]

(ii)Convert each molecule to a Molecular tree. First, we have to decompose the molecule to a tree.

Tree Decomposition of Molecules:

A tree decomposition maps a graph G into a junction tree by contracting certain vertices into a single node so that G becomes cycle-free. Formally, given a graph G, a junction tree TG = (V, E, X ) is a connected labeled tree whose node set is V = {C1, · · · , Cn} and edge set is E.Here X is vocabulary contains only cycles (rings) and single edges.

We first find simple cycles of given graph G, and its edges not belonging to any cycles.

Two simple rings are merged if they have more than two overlapping atoms. Each of those cycles or edges is considered as a cluster(clique).

Here cliques are nothing but the clusters. We will check the length of the clique and if it is more than 2, then we will check for the set of intersection atoms in the neighborhood list of the cluster. If the intersection atom list is more than 2 we will merge them.

    for i in range(len(cliques)):
        if len(cliques[i]) <= 2: continue
        for atom in cliques[i]:
            for j in nei_list[atom]:
                if i >= j or len(cliques[j]) <= 2: continue
                inter = set(cliques[i]) & set(cliques[j])
                if len(inter) > 2:
                    cliques[i] = list(set(cliques[i]))
                    cliques[j] = []
    cliques = [c for c in cliques if len(c) > 0]
    nei_list = [[] for i in range(n_atoms)]
    for i in range(len(cliques)):
        for atom in cliques[i]:

Next, a cluster graph is constructed by adding edges between all intersecting clusters. Finally, we select one of its spanning trees as the junction tree of G.

Here csr_matrix is creating a sparse matrix with a given number of rows and columns and minumum_spanning_tree is an inbuilt from scipy module to get the minimum spanning tree.

    row,col,data = zip(*edges)
    n_clique = len(cliques)
    clique_graph = csr_matrix( (data,(row,col)), shape=(n_clique,n_clique) )
    junc_tree = minimum_spanning_tree(clique_graph)

Now, after collecting cliques and edges from tree decomposition, we construct a molecular tree using those cliques and edges.

II.Defining the model

Here we illustrate our model as JTNNVAE.

class JTNNVAE(nn.Module):

    def __init__(self, vocab, hidden_size, latent_size, depthT, depthG):
        super(JTNNVAE, self).__init__()
        self.vocab = vocab
        self.hidden_size = int(hidden_size)
        self.latent_size = latent_size = latent_size / 2 #Tree and Mol has two vectors
        self.jtnn = JTNNEncoder(int(hidden_size),int(depthT), nn.Embedding(780,450))
        self.decoder = JTNNDecoder(vocab, int(hidden_size), int(latent_size), nn.Embedding(780,450))

        self.jtmpn = JTMPN(int(hidden_size), int(depthG))
        self.mpn = MPN(int(hidden_size), int(depthG))

        self.A_assm = nn.Linear(int(latent_size), int(hidden_size), bias=False)
        self.assm_loss = nn.CrossEntropyLoss(size_average=False)

        self.T_mean = nn.Linear(int(hidden_size), int(latent_size))
        self.T_var = nn.Linear(int(hidden_size), int(latent_size))
        self.G_mean = nn.Linear(int(hidden_size), int(latent_size))
        self.G_var = nn.Linear(int(hidden_size), int(latent_size))        


As we have already seen in the synopsis,first we have to encode the graph and then tree and then decode the tree and then finally decode the graph.This will help us to make our work easy.

Graph Encoder:

(i) We encode the latent representation of G by a graph message-passing network
. (ii)Each vertex v has a feature vector xv indicating the atom type, valence, and other properties. Similarly, each edge (u, v) ∈ E has a feature vector xuv indicating its bond type, and two hidden vectors νuv and νvu denoting the message from u to v and vice versa.

Here a1,a2 are two atoms having a bond. We get atom features from atom_features1. We also get bond features from bond_features1 function and we concatenate them to an existing dimension of the atom.

            for atom in mol.GetAtoms():
                fatoms.append( atom_features1(atom) )

            for bond in mol.GetBonds():
                a1 = bond.GetBeginAtom()
                a2 = bond.GetEndAtom()
                x = a1.GetIdx() + total_atoms
                y = a2.GetIdx() + total_atoms

                b = len(all_bonds) 
                fbonds.append([fatoms[x], bond_features1(bond)], 0) )

                b = len(all_bonds)
                fbonds.append([fatoms[y], bond_features1(bond)], 0) )
            total_atoms += n_atoms

(iii)After T steps of iteration, we aggregate those messages as the latent vector of each vertex.

Tree Encoder:

(i) We similarly encode TG with a tree message passing network.

We construct a node graph and message graph.Node graph contains the information that’s where the messages are connected to a index. The message graph contain information that which message is in the invert direction.

        for x,y in messages[1:]:
            mid1 = mess_dict[(x.idx,y.idx)]
            fmess[mid1] = x.idx 
            for z in y.neighbors:
                if z.idx == x.idx: continue
                mid2 = mess_dict[(y.idx,z.idx)]

(ii)In the first bottom-up phase, messages are initiated from the leaf nodes and propagated iteratively towards root.
(iii)In the top-down phase, messages are propagated from the root to all the leaf nodes.

Tree Decoder:

We decode a junction tree T from its encoding zT with a tree structured decoder.Our tree decoder traverses the entire tree from the root, and generates nodes in their depth-first order.

Tree Decoding Process
Tree Decoding Process

For every visited node, the decoder first makes a topological prediction whether this node has children to be generated. When a new child node is created, we predict its label and recurse this process. The decoder backtracks when a node has no more children to generate. Here we decode our tree and assemble the nodes in depth-first order.

Graph Decoder:

(i) The final step of our model is to reproduce a molecular graph G that underlies the predicted junction tree T.

(ii)We enumerate different combinations between red cluster C and its neighbors. Crossed arrows indicate combinations that lead to chemically infeasible molecules.
(iii) Rank subgraphs at each node. The final graph is decoded by putting together all the predicted subgraphs.

After training is done, save the model using

IV.Generating sample molecules

This is how we sample new molecules. First, load the saved model and generate the new text using sample_prior() function.

    for i in range(10):


Here are some samples I generated.


Thanks for reading!!! Happy learning! :)