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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

Therapeutic antibody candidates often require extensive engineering to improve key functional and developability properties before clinical development. This can be achieved through iterative design, where starting molecules are optimized…

Machine Learning · Computer Science 2025-09-23 Aniruddh Raghu , Sebastian Ober , Maxwell Kazman , Hunter Elliott

Current SMILES-based diffusion models for molecule generation typically support only unimodal constraint. They inject conditioning signals at the start of the training process and require retraining a new model from scratch whenever the…

Machine Learning · Computer Science 2025-08-21 Yunzhe Zhang , Yifei Wang , Khanh Vinh Nguyen , Pengyu Hong

Preference-conditioned image generation seeks to adapt generative models to individual users, producing outputs that reflect personal aesthetic choices beyond the given textual prompt. Despite recent progress, existing approaches either…

Computer Vision and Pattern Recognition · Computer Science 2025-12-09 Wenyi Mo , Tianyu Zhang , Yalong Bai , Ligong Han , Ying Ba , Dimitris N. Metaxas

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

Antibodies offer great potential for the treatment of various diseases. However, the discovery of therapeutic antibodies through traditional wet lab methods is expensive and time-consuming. The use of generative models in designing…

Denoising diffusion probabilistic models (DDPMs) are a recent family of generative models that achieve state-of-the-art results. In order to obtain class-conditional generation, it was suggested to guide the diffusion process by gradients…

Computer Vision and Pattern Recognition · Computer Science 2023-03-17 Bahjat Kawar , Roy Ganz , Michael Elad

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

Therapeutic antibodies require not only high-affinity target engagement, but also favorable manufacturability, stability, and safety profiles for clinical effectiveness. These properties are collectively called `developability'. To enable a…

Machine Learning · Computer Science 2025-07-04 Siqi Zhao , Joshua Moller , Porfi Quintero-Cadena , Lood van Niekerk

The adaptive immune response, largely mediated by B-cell receptors (BCRs), plays a crucial role for effective pathogen neutralization due to its diversity and antigen specificity. Designing BCRs de novo, or from scratch, has been…

Biomolecules · Quantitative Biology 2024-09-11 Desmond Kuan , Amir Barati Farimani

The conditional generation of proteins with desired functions is a key goal for generative models. Existing methods based on prompting of protein language models (PLMs) can generate proteins conditioned on a target functionality, such as a…

Biomolecules · Quantitative Biology 2025-06-13 Jason Yang , Aadyot Bhatnagar , Jeffrey A. Ruffolo , Ali Madani

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

Recent advances in diffusion models have shown remarkable potential in the conditional generation of novel molecules. These models can be guided in two ways: (i) explicitly, through additional features representing the condition, or (ii)…

Machine Learning · Computer Science 2025-03-12 Yuchen Shen , Chenhao Zhang , Sijie Fu , Chenghui Zhou , Newell Washburn , Barnabás Póczos

Controlling the behavior of language models (LMs) without re-training is a major open problem in natural language generation. While recent works have demonstrated successes on controlling simple sentence attributes (e.g., sentiment), there…

Computation and Language · Computer Science 2022-05-31 Xiang Lisa Li , John Thickstun , Ishaan Gulrajani , Percy Liang , Tatsunori B. Hashimoto

Generating novel and functional protein sequences is critical to a wide range of applications in biology. Recent advancements in conditional diffusion models have shown impressive empirical performance in protein generation tasks. However,…

Machine Learning · Computer Science 2025-12-04 Zinan Ling , Yi Shi , Brett McKinney , Da Yan , Yang Zhou , Bo Hui

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

Reparameterized diffusion models (RDMs) have recently matched autoregressive methods in protein generation, motivating their use for challenging tasks such as designing membrane proteins, which possess interleaved soluble and transmembrane…

Biomolecules · Quantitative Biology 2025-09-30 Shrey Goel , Peregrine M. Schray , Yinuo Zhang , Sophia Vincoff , Huong T. Kratochvil , Pranam Chatterjee

Proteins are shaped by gradual evolution under biophysical and functional constraints. Protein language models learn rich evolutionary constraints from large-scale sequences, and discrete diffusion-based protein language models~(\eg, DPLMs)…

Machine Learning · Computer Science 2026-05-14 Xinyou Wang , Liang Hong , Jiasheng Ye , Zaixiang Zheng , Yu Li , Shujian Huang , Quanquan Gu

Diffusion probabilistic models have achieved enormous success in the field of image generation and manipulation. In this paper, we explore a novel paradigm of using the diffusion model and classifier guidance in the latent semantic space…

Computer Vision and Pattern Recognition · Computer Science 2023-05-25 Changhao Shi , Haomiao Ni , Kai Li , Shaobo Han , Mingfu Liang , Martin Renqiang Min

Discrete diffusion models have recently emerged as strong alternatives to autoregressive language models, matching their performance through large-scale training. However, inference-time control remains relatively underexplored. In this…

Machine Learning · Computer Science 2026-04-09 Meihua Dang , Jiaqi Han , Minkai Xu , Kai Xu , Akash Srivastava , Stefano Ermon
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