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Designing proteins de novo with tailored structural, physicochemical, and functional properties remains a grand challenge in biotechnology, medicine, and materials science, due to the vastness of sequence space and the complex coupling…

Artificial Intelligence · Computer Science 2025-12-01 Fiona Y. Wang , Di Sheng Lee , David L. Kaplan , Markus J. Buehler

Protein language models (pLMs) pre-trained on vast protein sequence databases excel at various downstream tasks but often lack the structural knowledge essential for some biological applications. To address this, we introduce a method to…

Comprehending the long-timescale dynamics of protein-ligand complexes is very important for drug discovery and structural biology, but it continues to be computationally challenging for large biomolecular systems. We introduce…

Biomolecules · Quantitative Biology 2025-08-26 Rakesh Thakur , Riya Gupta

We introduce a protein language model for determining the complete sequence of a peptide based on measurement of a limited set of amino acids. To date, protein sequencing relies on mass spectrometry, with some novel edman degregation based…

Current protein language models (PLMs) learn protein representations mainly based on their sequences, thereby well capturing co-evolutionary information, but they are unable to explicitly acquire protein functions, which is the end goal of…

Biomolecules · Quantitative Biology 2023-07-06 Minghao Xu , Xinyu Yuan , Santiago Miret , Jian Tang

Text-guided molecule generation is a task where molecules are generated to match specific textual descriptions. Recently, most existing SMILES-based molecule generation methods rely on an autoregressive architecture. In this work, we…

Machine Learning · Computer Science 2024-02-21 Haisong Gong , Qiang Liu , Shu Wu , Liang Wang

Diffusion Language Models (DLMs) are rapidly emerging as a powerful and promising alternative to the dominant autoregressive (AR) paradigm. By generating tokens in parallel through an iterative denoising process, DLMs possess inherent…

Computation and Language · Computer Science 2025-12-08 Tianyi Li , Mingda Chen , Bowei Guo , Zhiqiang Shen

Molecular property prediction is a crucial foundation for drug discovery. In recent years, pre-trained deep learning models have been widely applied to this task. Some approaches that incorporate prior biological domain knowledge into the…

Machine Learning · Computer Science 2024-08-20 Tianyu Zhang , Yuxiang Ren , Chengbin Hou , Hairong Lv , Xuegong Zhang

We consider the protein sequence engineering problem, which aims to find protein sequences with high fitness levels, starting from a given wild-type sequence. Directed evolution has been a dominating paradigm in this field which has an…

Machine Learning · Computer Science 2025-01-20 Yinkai Wang , Jiaxing He , Yuanqi Du , Xiaohui Chen , Jianan Canal Li , Li-Ping Liu , Xiaolin Xu , Soha Hassoun

Denoising diffusion probabilistic models have recently demonstrated state-of-the-art generative performance and have been used as strong pixel-level representation learners. This paper decomposes the interrelation between the generative…

Computer Vision and Pattern Recognition · Computer Science 2024-04-16 Zixuan Pan , Jianxu Chen , Yiyu Shi

The design of protein sequences with desired functionalities is a fundamental task in protein engineering. Deep generative methods, such as autoregressive models and diffusion models, have greatly accelerated the discovery of novel protein…

Machine Learning · Computer Science 2025-04-16 Zitai Kong , Yiheng Zhu , Yinlong Xu , Hanjing Zhou , Mingzhe Yin , Jialu Wu , Hongxia Xu , Chang-Yu Hsieh , Tingjun Hou , Jian Wu

Proteins perform critical processes in all living systems: converting solar energy into chemical energy, replicating DNA, as the basis of highly performant materials, sensing and much more. While an incredible range of functionality has…

Biomolecules · Quantitative Biology 2021-09-29 Leonardo V. Castorina , Rokas Petrenas , Kartic Subr , Christopher W. Wood

While Masked Diffusion Language Models (MDLMs) relying on token masking and unmasking have shown promise in language modeling, their computational efficiency and generation flexibility remain constrained by the masking paradigm. In this…

Computation and Language · Computer Science 2026-03-26 Fangyu Ding , Ding Ding , Sijin Chen , Kaibo Wang , Peng Xu , Zijin Feng , Haoli Bai , Kai Han , Youliang Yan , Binhang Yuan , Jiacheng Sun

Protein inverse folding is a fundamental problem in bioinformatics, aiming to recover the amino acid sequences from a given protein backbone structure. Despite the success of existing methods, they struggle to fully capture the intricate…

Machine Learning · Computer Science 2024-12-13 Chenglin Wang , Yucheng Zhou , Zijie Zhai , Jianbing Shen , Kai Zhang

Proteins perform their biological functions through three-dimensional structures encoded by amino acid sequences, and ligand-binding protein co-design requires models that generate sequence-structure compatible proteins under explicit…

Biomolecules · Quantitative Biology 2026-05-28 Chen Wei , Fanding Xu , Minghao Sun , Zhiyuan Liu , Lin Wang , Tianrui Jia , Yihang Zhou , Yang Zhang

Proteins are fundamental biological entities that play a key role in life activities. The amino acid sequences of proteins can be folded into stable 3D structures in the real physicochemical world, forming a special kind of…

Machine Learning · Computer Science 2023-01-04 Lirong Wu , Yufei Huang , Haitao Lin , Stan Z. Li

Although diffusion language models (DLMs) are evolving quickly, many recent models converge on a set of shared components. These components, however, are distributed across ad-hoc research codebases or lack transparent implementations,…

Computation and Language · Computer Science 2026-02-27 Zhanhui Zhou , Lingjie Chen , Hanghang Tong , Dawn Song

Geometric deep learning has recently achieved great success in non-Euclidean domains, and learning on 3D structures of large biomolecules is emerging as a distinct research area. However, its efficacy is largely constrained due to the…

Machine Learning · Computer Science 2023-10-31 Fang Wu , Lirong Wu , Dragomir Radev , Jinbo Xu , Stan Z. Li

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…

Machine Learning · Computer Science 2025-06-10 Yuyan Ni , Shikun Feng , Haohan Chi , Bowen Zheng , Huan-ang Gao , Wei-Ying Ma , Zhi-Ming Ma , Yanyan Lan

Computational models starting from large ensembles of evolutionarily related protein sequences capture a representation of protein families and learn constraints associated to protein structure and function. They thus open the possibility…

Biomolecules · Quantitative Biology 2024-12-30 Damiano Sgarbossa , Umberto Lupo , Anne-Florence Bitbol