40 accepted papers
D-peptide binders targeting L-proteins have promising therapeutic potential. Despite rapid advances in machine learning-based target-conditioned peptide design, generating D-peptide binders remains largely unexplored. In this work, we show that by injecting axial features to E(3)-equivariant (polar)…
A significant portion of disease-relevant proteins remain undruggable due to shallow, flexible, or otherwise ill-defined binding pockets that hinder conventional molecule screening. Fragment-based drug discovery (FBDD) offers a promising alternative, as small, low-complexity fragments can flexibly e…
Protein-ligand binding prediction is central to virtual screening and affinity ranking, two fundamental tasks in drug discovery. While recent retrieval-based methods embed ligands and protein pockets into Euclidean space for similarity-based search, the geometry of Euclidean embeddings often fails t
Recent advances in 3D molecular modeling have achieved high-fidelity structural synthesis, yet these models often lack an explicit and manipulable representation space. To address this, MolFLAE introduced a fixed-dimensional, E(3)-equivariant latent space, providing a novel framework for molecular e…
Virtual screening (VS) is an essential task in drug discovery, focusing on the identification of small-molecule ligands that bind to specific protein pockets. Existing deep learning methods, from early regression models to recent contrastive learning approaches, primarily rely on structural data whi
Virtual screening (VS) is a critical component of modern drug discovery, yet most existing methods—whether physics-based or deep learning-based—are developed around *holo* protein structures with known ligand-bound pockets. Consequently, their performance degrades significantly on *apo* or predicted…
Structure-guided molecular generation is pivotal in early-stage drug discovery, enabling the design of compounds tailored to specific protein targets. However, despite recent advances in 3D generative modeling, particularly in improving docking scores, these methods often produce rare and intrinsica…
Cyclic peptides exhibit better binding affinity and proteolytic stability compared to their linear counterparts. However, the development of cyclic peptide design models is hindered by the scarcity of data. To address this, we introduce **CPSea**(**C**yclic **P**eptide **Sea**), a dataset of 2.71 mi…
Flexible docking, which predicts the binding conformations of both proteins and small molecules by modeling their structural flexibility, plays a vital role in structure-based drug design. Although recent generative approaches, particularly diffusion-based models, have shown promising results, they…
Medicinal chemists often optimize drugs considering their 3D structures and designing structurally distinct molecules that retain key features, such as shapes, pharmacophores, or chemical properties. Previous deep learning approaches address this through supervised tasks like molecule inpainting or…
Small molecules are vital to modern medicine, and accurately predicting their bioactivity against protein targets is crucial for therapeutic discovery and development. However, current machine learning models often rely on spurious features, leading to biased outcomes. Notably, a simple pocket-only…
Recent advances in structure-based drug design (SBDD) have produced surprising results, with models often generating molecules that achieve better Vina docking scores than actual ligands. However, these results are frequently overly optimistic due to the limitations of docking score accuracy and the…
Diffusion-based models have shown great promise in molecular generation but often require a large number of sampling steps to generate valid samples. In this paper, we introduce a novel Straight-Line Diffusion Model (SLDM) to tackle this problem, by formulating the diffusion process to follow a line…
Molecular generation and molecular property prediction are both crucial for drug discovery, but they are often developed independently. Inspired by recent studies, which demonstrate that diffusion model, a prominent generative approach, can learn meaningful data representations that enhance predicti…
Self-supervised learning has recently gained growing interest in molecular modeling for scientific tasks such as AI-assisted drug discovery. Current studies consider leveraging both 2D and 3D molecular structures for representation learning. However, relying on straightforward alignment strategies t…
The binding between proteins and ligands plays a crucial role in the realm of drug discovery. Previous deep learning approaches have shown promising results over traditional computationally intensive methods, but resulting in poor generalization due to limited supervised data. In this paper, we prop…
In the field of Structure-based Drug Design (SBDD), deep learning-based generative models have achieved outstanding performance in terms of docking score. However, further study shows that the existing molecular generative methods and docking scores both have lacked consideration in terms of specifi…
Pocket representations play a vital role in various biomedical applications, such as druggability estimation, ligand affinity prediction, and de novo drug design. While existing geometric features and pretrained representations have demonstrated promising results, they usually treat pockets independ…
While molecular pre-training has shown great potential in enhancing drug discovery, the lack of a solid physical interpretation in current methods raises concerns about whether the learned representation truly captures the underlying explanatory factors in observed data, ultimately resulting in limi…
Recently, a noticeable trend has emerged in developing pre-trained foundation models in the domains of CV and NLP. However, for molecular pre-training, there lacks a universal model capable of effectively applying to various categories of molecular tasks, since existing prevalent pre-training method…
Generating desirable molecular structures in 3D is a fundamental problem for drug discovery. Despite the considerable progress we have achieved, existing methods usually generate molecules in atom resolution and ignore intrinsic local structures such as rings, which leads to poor quality in generate…
Virtual screening, which identifies potential drugs from vast compound databases to bind with a particular protein pocket, is a critical step in AI-assisted drug discovery. Traditional docking methods are highly time-consuming, and can only work with a restricted search library in real-life applicat…
The generation of 3D molecules requires simultaneously deciding the categorical features (atom types) and continuous features (atom coordinates). Deep generative models, especially Diffusion Models (DMs), have demonstrated effectiveness in generating feature-rich geometries. However, existing DMs ty…
Coordinate denoising is a promising 3D molecular pre-training method, which has achieved remarkable performance in various downstream drug discovery tasks. Theoretically, the objective is equivalent to learning the force field, which is revealed helpful for downstream tasks. Nevertheless, there are…
Due to the dialogue characteristics of unstructured contexts and multi-parties with first-person perspective, many successful text summarization works have failed when dealing with dialogue summarization. In dialogue summarization task, the input dialogue is usually spoken style with ellipsis and co…
By inferring latent groups in the training data, recent works introduce invariant learning to the case where environment annotations are unavailable. Typically, learning group invariance under a majority/minority split is empirically shown to be effective in improving out-of-distribution generalizat…
Although exposure bias has been widely studied in some NLP tasks, it faces its unique challenges in dialogue response generation, the representative one-to-various generation scenario. In real human dialogue, there are many appropriate responses for the same context, not only with different expressi…
Information seeking is an essential step for open-domain question answering to efficiently gather evidence from a large corpus. Recently, iterative approaches have been proven to be effective for complex questions, by recursively retrieving new evidence at each step. However, almost all existing ite…
Knowledge data are massive and widespread in the real-world, which can serve as good external sources to enrich conversations. However, in knowledge-grounded conversations, current models still lack the fine-grained control over knowledge selection and integration with dialogues, which finally leads…
Despite the success of neural dialogue systems in achieving high performance on the leader-board, they cannot meet users’ requirements in practice, due to their poor reasoning skills. The underlying reason is that most neural dialogue models only capture the syntactic and semantic information, but f…
Ranked list truncation is of critical importance in a variety of professional information retrieval applications such as patent search or legal search. The goal is to dynamically determine the number of returned documents according to some user-defined objectives, in order to reach a balance between…
In product description generation (PDG), the user-cared aspect is critical for the recommendation system, which can not only improve user's experiences but also obtain more clicks. High-quality customer reviews can be considered as an ideal source to mine user-cared aspects. However, in reality, a l…
Recent text generation models are easy to generate relevant and fluent text for the given text, while lack of causal reasoning ability when we change some parts of the given text. Counterfactual story rewriting is a recently proposed task to test the causal reasoning ability for text generation mode…
Unsupervised style transfer models are mainly based on an inductive learning approach, which represents the style as embeddings, decoder parameters, or discriminator parameters and directly applies these general rules to the test cases. However, the lacking of parallel corpus hinders the ability of…
This paper defines a new visual reasoning paradigm by introducing an important factor, i.e. transformation. The motivation comes from the fact that most existing visual reasoning tasks, such as CLEVR in VQA, are solely defined to test how well the machine understands the concepts and relations withi…
Ensemble-based debiasing methods have been shown effective in mitigating the reliance of classifiers on specific dataset bias, by exploiting the output of a bias-only model to adjust the learning target. In this paper, we focus on the bias-only model in these ensemble-based methods, which plays an i…
Embedding-based evaluation measures have shown promising improvements on the correlation with human judgments in natural language generation. In these measures, various intrinsic metrics are used in the computation, including generalized precision, recall, F-score and the earth mover's distance. How…
Topic drift is a common phenomenon in multi-turn dialogue. Therefore, an ideal dialogue generation models should be able to capture the topic information of each context, detect the relevant context, and produce appropriate responses accordingly. However, existing models usually use word or sentence…
The Transformer is widely used in natural language processing tasks. To train a Transformer however, one usually needs a carefully designed learning rate warm-up stage, which is shown to be crucial to the final performance but will slow down the optimization and bring more hyper-parameter tunings. I…
The goal of text generation models is to fit the underlying real probability distribution of text. For performance evaluation, quality and diversity metrics are usually applied. However, it is still not clear to what extend can the quality-diversity evaluation reflect the distribution-fitting goal.…