The vocabulary Vconstructed by Algorithm 1 exhibits the following advantageous properties. Prior to the proof, we first present a clear observation of the created vocabulary V: Proposition A.2. Given any F,F V, for any their instances arising on an arbitrary molecule during the extraction process, either they are not spatially intersected F F =, or they contain each other: F F or F F. Now we prove each claim in the above theorem. We prove it by contradiction. If it is the former case, then Fi1 should be firstly extracted and then merged with other fragments to yield Fi2 which means i1 < i2, conflicting with the assumption.

Nevertheless, these methods usually rely on hand-crafted or external subgraph construction, andthesubgraph assembling depends solely onlocal arrangement.

Molecule generation is central to a variety of applications. Current attention has been paid to approaching the generation task as subgraph prediction and assembling. Nevertheless, these methods usually rely on hand-crafted or external subgraph construction, and the subgraph assembling depends solely on local arrangement. In this paper, we define a novel notion, principal subgraph, that is closely related to the informative pattern within molecules. Interestingly, our proposed merge-and-update subgraph extraction method can automatically discover frequent principal subgraphs from the dataset, while previous methods are incapable of. Moreover, we develop a two-step subgraph assembling strategy, which first predicts a set of subgraphs in a sequence-wise manner and then assembles all generated subgraphs globally as the final output molecule. Built upon graph variational auto-encoder, our model is demonstrated to be effective in terms of several evaluation metrics and efficiency, compared with state-of-the-art methods on distribution learning and (constrained) property optimization tasks.