24 accepted papers
The training paradigm for large language models (LLMs) is moving from static datasets to experience-based learning, where agents acquire skills via interacting with complex environments. To facilitate this transition we introduce GEM (General Experience Maker), an open-source environment simulator d…
The recent paradigm shift towards training large language models (LLMs) using DeepSeek-R1-Zero-style reinforcement learning (RL) on verifiable rewards has led to impressive advancements in code and mathematical reasoning. However, this methodology is limited to tasks where rule-based answer verifica…
Reinforcement learning (RL) has become a cornerstone for fine-tuning Large Language Models (LLMs), with Proximal Policy Optimization (PPO) serving as the de facto standard algorithm. Despite its ubiquity, we argue that the core ratio clipping mechanism in PPO is structurally ill-suited for the large…
We introduce a **variational reasoning** framework for language models that treats thinking traces as latent variables and optimizes them through variational inference. Starting from the evidence lower bound (ELBO), we extend it to a multi-trace objective for tighter bounds and propose a forward-KL…
Accurate molecular representations are critical for drug discovery, and a central challenge lies in capturing the chemical environment of molecular fragments, as key interactions, such as H-bond and π stacking—occur only under specific local conditions. Most existing approaches represent molecules a…
Proteins typically exist in complexes, interacting with other proteins or biomolecules to perform their specific biological roles. Research on single-chain protein modeling has been extensively and deeply explored, with advancements seen in models like the series of ESM and AlphaFold2. Despite these…
Cyclic peptides offer inherent advantages in pharmaceuticals. For example, cyclic peptides are more resistant to enzymatic hydrolysis compared to linear peptides and usually exhibit excellent stability and affinity. Although deep generative models have achieved great success in linear peptide design…
Molecular docking is a key task in computational biology that has attracted increasing interest from the machine learning community. While existing methods have achieved success, they generally treat each protein-ligand pair in isolation. Inspired by the biochemical observation that ligands binding…
The dynamic nature of proteins, influenced by ligand interactions, is essential for comprehending protein function and progressing drug discovery. Traditional structure-based drug design (SBDD) approaches typically target binding sites with rigid structures, limiting their practical application in d…
Understanding the various properties of glycans with machine learning has shown some preliminary promise. However, previous methods mainly focused on modeling the backbone structure of glycans as graphs of monosaccharides (i.e., sugar units), while they neglected the atomic structures underlying eac…
The dream to create AI assistants as capable and versatile as the fictional J.A.R.V.I.S from Iron Man has long captivated imaginations. With the evolution of multi-modal large language models ((M)LLMs), this dream is closer to reality, as (M)LLM-based Agents using computers, mobile phones and web br…
Recent years have witnessed a surge in the development of protein foundation models, significantly improving performance in protein prediction and generative tasks ranging from 3D structure prediction and protein design to conformational dynamics. However, the capabilities and limitations associated…
Consistency models are a class of generative models that enable few-step generation for diffusion and flow matching models. While consistency models have achieved promising results on Euclidean domains like images, their applications to Riemannian manifolds remain challenging due to the curved geome…
Drug discovery is crucial for identifying candidate drugs for various diseases. However, its low success rate often results in a scarcity of annotations, posing a few-shot learning problem. Existing methods primarily focus on single-scale features, overlooking the hierarchical molecular structures t…
Antibody design, a crucial task with significant implications across various disciplines such as therapeutics and biology, presents considerable challenges due to its intricate nature. In this paper, we tackle antigen-specific antibody sequence-structure co-design as an optimization problem towards…
Structure-based drug design (SBDD) aims to generate 3D ligand molecules that bind to specific protein targets. Existing 3D deep generative models including diffusion models have shown great promise for SBDD. However, it is complex to capture the essential protein-ligand interactions exactly in 3D sp…
Recently, 3D generative models have shown promising performances in structure-based drug design by learning to generate ligands given target binding sites. However, only modeling the target-ligand distribution can hardly fulfill one of the main goals in drug discovery -- designing novel ligands with…
Generating ligand molecules that bind to specific protein targets via generative models holds substantial promise for advancing structure-based drug design. Existing methods generate molecules from scratch without reference or template ligands, which poses challenges in model optimization and may yi…
Generating 3D ligand molecules that bind to specific protein targets via diffusion models has shown great promise for structure-based drug design. The key idea is to disrupt molecules into noise through a fixed forward process and learn its reverse process to generate molecules from noise in a denoi…
Dual-target therapeutic strategies have become a compelling approach and attracted significant attention due to various benefits, such as their potential in overcoming drug resistance in cancer therapy. Considering the tremendous success that deep generative models have achieved in structure-based d…
Considering generating samples with high rewards, we focus on optimizing deep neural networks parameterized stochastic differential equations (SDEs), the advanced generative models with high expressiveness, with policy gradient, the leading algorithm in reinforcement learning. Nevertheless, when app…
Designing 3D ligands within a target binding site is a fundamental task in drug discovery. Existing structured-based drug design methods treat all ligand atoms equally, which ignores different roles of atoms in the ligand for drug design and can be less efficient for exploring the large drug-like mo…
Graph Structure Learning (GSL) has recently garnered considerable attention due to its ability to optimize both the parameters of Graph Neural Networks (GNNs) and the computation graph structure simultaneously. Despite the proliferation of GSL methods developed in recent years, there is no standard…
Deep Neural Network (DNN) is powerful but computationally expensive and memory intensive, thus impeding its practical usage on resource-constrained front-end devices. DNN pruning is an approach for deep model compression, which aims at eliminating some parameters with tolerable performance degradati…