Molecular pretrained representations (MPR) has emerged as a powerful approach for addressing the challenge of limited supervised data in applications such as drug discovery and material design. While early MPR methods relied on 1D sequences and 2D graphs, recent advancements have incorporated 3D conformational information to capture rich atomic interactions. However, these prior models treat molecules merely as discrete atom sets, overlooking the space surrounding them. We argue from a physical perspective that only modeling these discrete points is insufficient. We first present a simple yet insightful observation: naively adding randomly sampled virtual points beyond atoms can surprisingly enhance MPR performance. In light of this, we propose a principled framework that incorporates the entire 3D space spanned by molecules. We implement the framework via a novel Transformer-based architecture, dubbed SpaceFormer, with three key components: (1)grid-based space discretization; (2)grid sampling/merging; and (3)efficient 3D positional encoding. Extensive experiments show that SpaceFormer significantly outperforms previous 3D MPR models across various downstream tasks with limited data, validating the benefit of leveraging the additional 3D space beyond atoms in MPR models.

In recent years, there has been a surge in the development of 3D structure-based pre-trained protein models, representing a significant advancement over pre-trained protein language models in various downstream tasks. However, most existing structure-based pre-trained models primarily focus on the residue level, i.e., alpha carbon atoms, while ignoring other atoms like side chain atoms. We argue that modeling proteins at both residue and atom levels is important since the side chain atoms can also be crucial for numerous downstream tasks, for example, molecular docking. Nevertheless, we find that naively combining residue and atom information during pre-training typically fails. We identify a key reason is the information leakage caused by the inclusion of atom structure in the input, which renders residue-level pre-training tasks trivial and results in insufficiently expressive residue representations. To address this issue, we introduce a span mask pre-training strategy on 3D protein chains to learn meaningful representations of both residues and atoms. This leads to a simple yet effective approach to learning protein representation suitable for diverse downstream tasks. Extensive experimental results on binding site prediction and function prediction tasks demonstrate our proposed pre-training approach significantly outperforms other methods. Our code will be made public.

Molecular perception aims to construct 3D molecules from 3D atom clouds (i.e., atom types and corresponding 3D coordinates), determining bond connections, bond orders, and other molecular attributes within molecules. It is essential for realizing many applications in cheminformatics and bioinformatics, such as modeling quantum chemistry-derived molecular structures in protein-ligand complexes. Additionally, many molecular generation methods can only generate molecular 3D atom clouds, requiring molecular perception as a necessary post-processing. However, existing molecular perception methods mainly rely on predefined chemical rules and fail to leverage 3D geometric information, whose performance is sub-optimal fully. In this study, we propose MPerformer, an SE(3) Transformer-based molecular perceptron exhibiting SE(3)-invariance, to construct 3D molecules from 3D atom clouds efficiently. Besides, we propose a multi-task pretraining-and-finetuning paradigm to learn this model. In the pretraining phase, we jointly minimize an attribute prediction loss and an atom cloud reconstruction loss, mitigating the data imbalance issue of molecular attributes and enhancing the robustness and generalizability of the model. Experiments show that MPerformer significantly outperforms state-of-the-art molecular perception methods in precision and robustness, benefiting various molecular generation scenarios.

Shuqi Lu, Di He, Chenyan Xiong, Guolin Ke, Waleed Malik, Zhicheng Dou, Paul Bennett, Tie-Yan Liu, Arnold Overwijk. Proceedings of the 2021 Conference on Empirical Methods in Natural Language Processing. 2021.

Search result diversification aims to retrieve diverse results to cover as many subtopics related to the query as possible. Recent studies showed that supervised diversification models are able to outperform the heuristic approaches, by automatically learning a diversification function other than using manually designed score functions. The main challenge of training a diversification model is the lack of high-quality training samples. Due to the involvement of dependence between documents in the ranker, it is very hard for training algorithms to select effective positive and negative ranking lists to train a reliable ranking model, given a large number of candidate documents within which different documents are relevant to different subtopics. To tackle this problem, we propose a supervised diversification framework based on Generative Adversarial Network (GAN). It consists of a generator and a discriminator interacting with each other in a minimax game. Specifically, the generator generates more confusing negative samples for the discriminator, and the discriminator sends back complementary ranking signals to the generator. Furthermore, we explicitly exploit subtopics in the generator, whereas focusing on modeling document similarity in the discriminator. Through such a minimax game, we are able to obtain better ranking models by combining ranking signals learned by the generator and the discriminator. Experimental results on the TREC Web Track dataset show that the proposed method can significantly outperform existing diversification methods.

This paper presents a knowledge graph enhanced personalized search model, KEPS. For each user and her queries, KEPS first con- ducts personalized entity linking on the queries and forms better intent representations; then it builds a knowledge enhanced profile for the user, using memory networks to store the predicted search intents and linked entities in her search history. The knowledge enhanced user profile and intent representation are then utilized by KEPS for better, knowledge enhanced, personalized search. Furthermore, after providing personalized search for each query, KEPS leverages user's feedback (click on documents) to post-adjust the entity linking on previous queries. This fixes previous linking errors and improves ranking quality for future queries. Experiments on the public AOL search log demonstrate the advantage of knowledge in personalized search: personalized entity linking better reflects user's search intent, the memory networks better maintain user's subtle preferences, and the post linking adjustment fixes some linking errors with the received feedback signals. The three components together lead to a significantly better ranking accuracy of KEPS.

Personalized search aims to adapt document ranking to user's personal interests. Traditionally, this is done by extracting click and topical features from historical data in order to construct a user profile. In recent years, deep learning has been successfully used in personalized search due to its ability of automatic feature learning. However, the small amount of noisy personal data poses challenges to deep learning models to learn the personalized classification boundary between relevant and irrelevant results. In this paper, we propose PSGAN, a Generative Adversarial Network (GAN) framework for personalized search. By means of adversarial training, we enforce the model to pay more attention to training data that are difficult to distinguish. We use the discriminator to evaluate personalized relevance of documents and use the generator to learn the distribution of relevant documents. Two alternative ways to construct the generator in the framework are tested: based on the current query or based on a set of generated queries. Experiments on data from a commercial search engine show that our models can yield significant improvements over state-of-the-art models.