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This paper introduces diffusion protein language model (DPLM), a versatile protein language model that demonstrates strong generative and predictive capabilities for protein sequences. We first pre-train scalable DPLMs from…

Machine Learning · Computer Science 2024-10-17 Xinyou Wang , Zaixiang Zheng , Fei Ye , Dongyu Xue , Shujian Huang , Quanquan Gu

Proteins are fundamental to biology, executing diverse functions through complex physicochemical interactions, and they hold transformative potential across medicine, materials science, and environmental applications. Protein Language…

Biomolecules · Quantitative Biology 2025-06-11 Logan Hallee , Nikolaos Rafailidis , David B. Bichara , Jason P. Gleghorn

Proteins are essential macromolecules defined by their amino acid sequences, which determine their three-dimensional structures and, consequently, their functions in all living organisms. Therefore, generative protein modeling necessitates…

Machine Learning · Computer Science 2024-10-18 Xinyou Wang , Zaixiang Zheng , Fei Ye , Dongyu Xue , Shujian Huang , Quanquan Gu

We introduce EvoFlows, a variable-length protein sequence-to-sequence modeling approach designed for protein engineering. Existing protein language models are poorly suited for optimization tasks: autoregressive models require full sequence…

Machine Learning · Computer Science 2026-04-09 Nicolas Deutschmann , Constance Ferragu , Jonathan D. Ziegler , Shayan Aziznejad , Eli Bixby

Diffusion Language Models (DLMs) offer a promising alternative for language modeling by enabling parallel decoding through iterative refinement. However, most DLMs rely on hard binary masking and discrete token assignments, which hinder the…

Computation and Language · Computer Science 2026-01-19 Linhao Zhong , Linyu Wu , Bozhen Fang , Tianjian Feng , Chenchen Jing , Wen Wang , Jiaheng Zhang , Hao Chen , Chunhua Shen

A long-standing goal of machine-learning-based protein engineering is to accelerate the discovery of novel mutations that improve the function of a known protein. We introduce a sampling framework for evolving proteins in silico that…

Machine Learning · Computer Science 2023-04-10 Patrick Emami , Aidan Perreault , Jeffrey Law , David Biagioni , Peter C. St. John

We introduce \textbf{Evo}, a duality latent trajectory model that bridges autoregressive (AR) and diffusion-based language generation within a continuous evolutionary generative framework. Rather than treating AR decoding and diffusion…

Machine Learning · Computer Science 2026-03-10 Junde Wu , Minhao Hu , Jiayuan Zhu , Yuyuan Liu , Tianyi Zhang , Kang Li , Jingkun Chen , Jiazhen Pan , Min Xu , Yueming Jin

Proteins adopt multiple structural conformations to perform their diverse biological functions, and understanding these conformations is crucial for advancing drug discovery. Traditional physics-based simulation methods often struggle with…

Biomolecules · Quantitative Biology 2025-03-14 Jiarui Lu , Xiaoyin Chen , Stephen Zhewen Lu , Chence Shi , Hongyu Guo , Yoshua Bengio , Jian Tang

Predicting the fitness impact of mutations is central to protein engineering but constrained by limited assays relative to the size of sequence space. Protein language models (pLMs) trained with masked language modeling (MLM) exhibit strong…

Machine Learning · Computer Science 2026-04-14 Jigang Fan , Xiaoran Jiao , Shengdong Lin , Zhanming Liang , Weian Mao , Chenchen Jing , Hao Chen , Chunhua Shen

Current Large Language Models (LLMs) for understanding proteins primarily treats amino acid sequences as a text modality. Meanwhile, Protein Language Models (PLMs), such as ESM-2, have learned massive sequential evolutionary knowledge from…

Machine Learning · Computer Science 2024-12-17 Nuowei Liu , Changzhi Sun , Tao Ji , Junfeng Tian , Jianxin Tang , Yuanbin Wu , Man Lan

Antibody therapeutics are among the most successful modern medicines, yet computationally designing antibodies with desirable binding and developability properties remains challenging. While protein language models (pLMs) have emerged as…

Machine Learning · Computer Science 2026-05-11 Justin Sanders , Luca Giancardo , Lan Guo , Yue Zhao , Kemal Sonmez , Nina Cheng , Melih Yilmaz

Directed evolution is a versatile technique in protein engineering that mimics the process of natural selection by iteratively alternating between mutagenesis and screening in order to search for sequences that optimize a given property of…

Biomolecules · Quantitative Biology 2024-05-02 Lixue Cheng , Ziyi Yang , Changyu Hsieh , Benben Liao , Shengyu Zhang

Large Language Models (LLMs) have achieved remarkable success in natural language processing tasks, but their massive size and computational demands hinder their deployment in resource-constrained environments. Existing model pruning…

Computation and Language · Computer Science 2025-08-14 Shangyu Wu , Hongchao Du , Ying Xiong , Shuai Chen , Tei-Wei Kuo , Nan Guan , Chun Jason Xue

Directed evolution is an iterative laboratory process of designing proteins with improved function by iteratively synthesizing new protein variants and evaluating their desired property with expensive and time-consuming biochemical…

Machine Learning · Computer Science 2025-09-08 Matouš Soldát , Jiří Kléma

Protein design with desirable properties has been a significant challenge for many decades. Generative artificial intelligence is a promising approach and has achieved great success in various protein generation tasks. Notably, diffusion…

With the exponential increase of the protein sequence databases over time, multiple-sequence alignment (MSA) methods, like PSI-BLAST, perform exhaustive and time-consuming database search to retrieve evolutionary information. The resulting…

Quantitative Methods · Quantitative Biology 2023-08-21 Issar Arab

Early DNA foundation models adopted BERT-style training, achieving good performance on DNA understanding tasks but lacking generative capabilities. Recent autoregressive models enable DNA generation, but employ left-to-right causal modeling…

Machine Learning · Computer Science 2026-03-03 Zhao Yang , Hengchang Liu , Chuan Cao , Bing Su

In a convergence of machine learning and biology, we reveal that diffusion models are evolutionary algorithms. By considering evolution as a denoising process and reversed evolution as diffusion, we mathematically demonstrate that diffusion…

Neural and Evolutionary Computing · Computer Science 2026-05-12 Yanbo Zhang , Benedikt Hartl , Hananel Hazan , Michael Levin

Predicting protein properties is paramount for biological and medical advancements. Current protein engineering mutates on a typical protein, called the wild-type, to construct a family of homologous proteins and study their properties.…

Machine Learning · Computer Science 2024-06-26 Zhiqiang Zhong , Davide Mottin

While chain-of-thought (CoT) distillation from advanced large language models (LLMs) has proven effective in general reasoning tasks, it struggles in scientific domains where even advanced models often produce incorrect or superficial…

Computation and Language · Computer Science 2025-10-17 Kehua Feng , Keyan Ding , Zhihui Zhu , Lei Liang , Qiang Zhang , Huajun Chen
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