Liang He

Lang Yu, Zhangyang Gao, Cheng Tan et al.

SE(3)-based generative models have shown great promise in protein geometry modeling and effective structure design. However, the field currently lacks a modularized benchmark to enable comprehensive investigation and fair comparison of different methods. In this paper, we propose Protein-SE(3), a new benchmark based on a unified training framework, which comprises protein scaffolding tasks, integrated generative models, high-level mathematical abstraction, and diverse evaluation metrics. Recent advanced generative models designed for protein scaffolding, from multiple perspectives like DDPM (Genie1 and Genie2), Score Matching (FrameDiff and RfDiffusion) and Flow Matching (FoldFlow and FrameFlow) are integrated into our framework. All integrated methods are fairly investigated with the same training dataset and evaluation metrics. Furthermore, we provide a high-level abstraction of the mathematical foundations behind the generative models, enabling fast prototyping of future algorithms without reliance on explicit protein structures. Accordingly, we release the first comprehensive benchmark built upon unified training framework for SE(3)-based protein structure design, which is publicly accessible at https://github.com/BruthYU/protein-se3.

Wentao Xu, Shun Zheng, Liang He et al.

In recent years, knowledge graph embedding becomes a pretty hot research topic of artificial intelligence and plays increasingly vital roles in various downstream applications, such as recommendation and question answering. However, existing methods for knowledge graph embedding can not make a proper trade-off between the model complexity and the model expressiveness, which makes them still far from satisfactory. To mitigate this problem, we propose a lightweight modeling framework that can achieve highly competitive relational expressiveness without increasing the model complexity. Our framework focuses on the design of scoring functions and highlights two critical characteristics: 1) facilitating sufficient feature interactions; 2) preserving both symmetry and antisymmetry properties of relations. It is noteworthy that owing to the general and elegant design of scoring functions, our framework can incorporate many famous existing methods as special cases. Moreover, extensive experiments on public benchmarks demonstrate the efficiency and effectiveness of our framework. Source codes and data can be found at \url{https://github.com/Wentao-Xu/SEEK}.

Xin Yi, Shunfan Zheng, Linlin Wang et al.

The current safeguard mechanisms for large language models (LLMs) are indeed susceptible to jailbreak attacks, making them inherently fragile. Even the process of fine-tuning on apparently benign data for downstream tasks can jeopardize safety. One potential solution is to conduct safety fine-tuning subsequent to downstream fine-tuning. However, there's a risk of catastrophic forgetting during safety fine-tuning, where LLMs may regain safety measures but lose the task-specific knowledge acquired during downstream fine-tuning. In this paper, we introduce a safety realignment framework through subspace-oriented model fusion (SOMF), aiming to combine the safeguard capabilities of initially aligned model and the current fine-tuned model into a realigned model. Our approach begins by disentangling all task vectors from the weights of each fine-tuned model. We then identify safety-related regions within these vectors by subspace masking techniques. Finally, we explore the fusion of the initial safely aligned LLM with all task vectors based on the identified safety subspace. We validate that our safety realignment framework satisfies the safety requirements of a single fine-tuned model as well as multiple models during their fusion. Our findings confirm that SOMF preserves safety without notably compromising performance on downstream tasks, including instruction following in Chinese, English, and Hindi, as well as problem-solving capabilities in Code and Math.

Yangzhe Peng, Kaiyuan Gao, Liang He et al.

Molecular docking plays a crucial role in predicting the binding mode of ligands to target proteins, and covalent interactions, which involve the formation of a covalent bond between the ligand and the target, are particularly valuable due to their strong, enduring binding nature. However, most existing docking methods and deep learning approaches hardly account for the formation of covalent bonds and the associated structural changes. To address this gap, we introduce a comprehensive benchmark for covalent docking, CovDocker, which is designed to better capture the complexities of covalent binding. We decompose the covalent docking process into three main tasks: reactive location prediction, covalent reaction prediction, and covalent docking. By adapting state-of-the-art models, such as Uni-Mol and Chemformer, we establish baseline performances and demonstrate the effectiveness of the benchmark in accurately predicting interaction sites and modeling the molecular transformations involved in covalent binding. These results confirm the role of the benchmark as a rigorous framework for advancing research in covalent drug design. It underscores the potential of data-driven approaches to accelerate the discovery of selective covalent inhibitors and addresses critical challenges in therapeutic development.

Liang He, Shizhuo Zhang, Lijun Wu et al.

Understanding protein sequences is vital and urgent for biology, healthcare, and medicine. Labeling approaches are expensive yet time-consuming, while the amount of unlabeled data is increasing quite faster than that of the labeled data due to low-cost, high-throughput sequencing methods. In order to extract knowledge from these unlabeled data, representation learning is of significant value for protein-related tasks and has great potential for helping us learn more about protein functions and structures. The key problem in the protein sequence representation learning is to capture the co-evolutionary information reflected by the inter-residue co-variation in the sequences. Instead of leveraging multiple sequence alignment as is usually done, we propose a novel method to capture this information directly by pre-training via a dedicated language model, i.e., Pairwise Masked Language Model (PMLM). In a conventional masked language model, the masked tokens are modeled by conditioning on the unmasked tokens only, but processed independently to each other. However, our proposed PMLM takes the dependency among masked tokens into consideration, i.e., the probability of a token pair is not equal to the product of the probability of the two tokens. By applying this model, the pre-trained encoder is able to generate a better representation for protein sequences. Our result shows that the proposed method can effectively capture the inter-residue correlations and improves the performance of contact prediction by up to 9% compared to the MLM baseline under the same setting. The proposed model also significantly outperforms the MSA baseline by more than 7% on the TAPE contact prediction benchmark when pre-trained on a subset of the sequence database which the MSA is generated from, revealing the potential of the sequence pre-training method to surpass MSA based methods in general.

Siyuan Liu, Yusong Wang, Tong Wang et al.

The identification of active binding drugs for target proteins (termed as drug-target interaction prediction) is the key challenge in virtual screening, which plays an essential role in drug discovery. Although recent deep learning-based approaches achieved better performance than molecular docking, existing models often neglect certain aspects of the intermolecular information, hindering the performance of prediction. We recognize this problem and propose a novel approach named Intermolecular Graph Transformer (IGT) that employs a dedicated attention mechanism to model intermolecular information with a three-way Transformer-based architecture. IGT outperforms state-of-the-art approaches by 9.1% and 20.5% over the second best for binding activity and binding pose prediction respectively, and shows superior generalization ability to unseen receptor proteins. Furthermore, IGT exhibits promising drug screening ability against SARS-CoV-2 by identifying 83.1% active drugs that have been validated by wet-lab experiments with near-native predicted binding poses.

Robert Ridley, Liang He, Xinyu Dai et al.

Cross-prompt automated essay scoring (AES) requires the system to use non target-prompt essays to award scores to a target-prompt essay. Since obtaining a large quantity of pre-graded essays to a particular prompt is often difficult and unrealistic, the task of cross-prompt AES is vital for the development of real-world AES systems, yet it remains an under-explored area of research. Models designed for prompt-specific AES rely heavily on prompt-specific knowledge and perform poorly in the cross-prompt setting, whereas current approaches to cross-prompt AES either require a certain quantity of labelled target-prompt essays or require a large quantity of unlabelled target-prompt essays to perform transfer learning in a multi-step manner. To address these issues, we introduce Prompt Agnostic Essay Scorer (PAES) for cross-prompt AES. Our method requires no access to labelled or unlabelled target-prompt data during training and is a single-stage approach. PAES is easy to apply in practice and achieves state-of-the-art performance on the Automated Student Assessment Prize (ASAP) dataset.

Xiangcheng Du, Tianlong Ma, Yingbin Zheng et al.

Texts from scene images typically consist of several characters and exhibit a characteristic sequence structure. Existing methods capture the structure with the sequence-to-sequence models by an encoder to have the visual representations and then a decoder to translate the features into the label sequence. In this paper, we study text recognition framework by considering the long-term temporal dependencies in the encoder stage. We demonstrate that the proposed Temporal Convolutional Encoder with increased sequential extents improves the accuracy of text recognition. We also study the impact of different attention modules in convolutional blocks for learning accurate text representations. We conduct comparisons on seven datasets and the experiments demonstrate the effectiveness of our proposed approach.