Jinhua Zhu

Qizhi Pei, Kaiyuan Gao, Lijun Wu et al.

Modeling the interaction between proteins and ligands and accurately predicting their binding structures is a critical yet challenging task in drug discovery. Recent advancements in deep learning have shown promise in addressing this challenge, with sampling-based and regression-based methods emerging as two prominent approaches. However, these methods have notable limitations. Sampling-based methods often suffer from low efficiency due to the need for generating multiple candidate structures for selection. On the other hand, regression-based methods offer fast predictions but may experience decreased accuracy. Additionally, the variation in protein sizes often requires external modules for selecting suitable binding pockets, further impacting efficiency. In this work, we propose $\mathbf{FABind}$, an end-to-end model that combines pocket prediction and docking to achieve accurate and fast protein-ligand binding. $\mathbf{FABind}$ incorporates a unique ligand-informed pocket prediction module, which is also leveraged for docking pose estimation. The model further enhances the docking process by incrementally integrating the predicted pocket to optimize protein-ligand binding, reducing discrepancies between training and inference. Through extensive experiments on benchmark datasets, our proposed $\mathbf{FABind}$ demonstrates strong advantages in terms of effectiveness and efficiency compared to existing methods. Our code is available at https://github.com/QizhiPei/FABind

Qizhi Pei, Wei Zhang, Jinhua Zhu et al.

Recent advancements in biological research leverage the integration of molecules, proteins, and natural language to enhance drug discovery. However, current models exhibit several limitations, such as the generation of invalid molecular SMILES, underutilization of contextual information, and equal treatment of structured and unstructured knowledge. To address these issues, we propose $\mathbf{BioT5}$, a comprehensive pre-training framework that enriches cross-modal integration in biology with chemical knowledge and natural language associations. $\mathbf{BioT5}$ utilizes SELFIES for $100%$ robust molecular representations and extracts knowledge from the surrounding context of bio-entities in unstructured biological literature. Furthermore, $\mathbf{BioT5}$ distinguishes between structured and unstructured knowledge, leading to more effective utilization of information. After fine-tuning, BioT5 shows superior performance across a wide range of tasks, demonstrating its strong capability of capturing underlying relations and properties of bio-entities. Our code is available at $\href{https://github.com/QizhiPei/BioT5}{Github}$.

Zongmeng Zhang, Jinhua Zhu, Wengang Zhou et al.

Dense retrieval, which aims to encode the semantic information of arbitrary text into dense vector representations or embeddings, has emerged as an effective and efficient paradigm for text retrieval, consequently becoming an essential component in various natural language processing systems. These systems typically focus on optimizing the embedding space by attending to the relevance of text pairs, while overlooking the Boolean logic inherent in language, which may not be captured by current training objectives. In this work, we first investigate whether current retrieval systems can comprehend the Boolean logic implied in language. To answer this question, we formulate the task of Boolean Dense Retrieval and collect a benchmark dataset, BoolQuestions, which covers complex queries containing basic Boolean logic and corresponding annotated passages. Through extensive experimental results on the proposed task and benchmark dataset, we draw the conclusion that current dense retrieval systems do not fully understand Boolean logic in language, and there is a long way to go to improve our dense retrieval systems. Furthermore, to promote further research on enhancing the understanding of Boolean logic for language models, we explore Boolean operation on decomposed query and propose a contrastive continual training method that serves as a strong baseline for the research community.

Zongmeng Zhang, Yufeng Shi, Jinhua Zhu et al.

Trustworthiness is an essential prerequisite for the real-world application of large language models. In this paper, we focus on the trustworthiness of language models with respect to retrieval augmentation. Despite being supported with external evidence, retrieval-augmented generation still suffers from hallucinations, one primary cause of which is the conflict between contextual and parametric knowledge. We deem that retrieval-augmented language models have the inherent capabilities of supplying response according to both contextual and parametric knowledge. Inspired by aligning language models with human preference, we take the first step towards aligning retrieval-augmented language models to a status where it responds relying merely on the external evidence and disregards the interference of parametric knowledge. Specifically, we propose a reinforcement learning based algorithm Trustworthy-Alignment, theoretically and experimentally demonstrating large language models' capability of reaching a trustworthy status without explicit supervision on how to respond. Our work highlights the potential of large language models on exploring its intrinsic abilities by its own and expands the application scenarios of alignment from fulfilling human preference to creating trustworthy agents.