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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

Recent advancements in machine learning techniques for protein folding motivate better results in its inverse problem -- protein design. In this work we introduce a new graph mimetic neural network, MimNet, and show that it is possible to…

Biomolecules · Quantitative Biology 2021-02-09 Moshe Eliasof , Tue Boesen , Eldad Haber , Chen Keasar , Eran Treister

Learning on 3D structures of large biomolecules is emerging as a distinct area in machine learning, but there has yet to emerge a unifying network architecture that simultaneously leverages the graph-structured and geometric aspects of the…

Biomolecules · Quantitative Biology 2021-05-18 Bowen Jing , Stephan Eismann , Patricia Suriana , Raphael J. L. Townshend , Ron Dror

Protein language models (pLMs) have demonstrated success at generating functional proteins across vast sequence spaces but lack the ability to design high-fitness variants on demand. Here, we iteratively guide pLMs toward user-defined…

Biomolecules · Quantitative Biology 2025-12-01 Filippo Stocco , Maria Artigues-Lleixa , Andrea Hunklinger , Talal Widatalla , Marc Guell , Noelia Ferruz

Protein diffusion models have emerged as a promising approach for protein design. One such pioneering model is Genie, a method that asymmetrically represents protein structures during the forward and backward processes, using simple…

Biomolecules · Quantitative Biology 2024-05-27 Yeqing Lin , Minji Lee , Zhao Zhang , Mohammed AlQuraishi

Protein structure-based property prediction has emerged as a promising approach for various biological tasks, such as protein function prediction and sub-cellular location estimation. The existing methods highly rely on experimental protein…

Machine Learning · Computer Science 2023-10-20 Yufei Huang , Siyuan Li , Jin Su , Lirong Wu , Odin Zhang , Haitao Lin , Jingqi Qi , Zihan Liu , Zhangyang Gao , Yuyang Liu , Jiangbin Zheng , Stan. ZQ. Li

Proteins power a vast array of functional processes in living cells. The capability to create new proteins with designed structures and functions would thus enable the engineering of cellular behavior and development of protein-based…

Biomolecules · Quantitative Biology 2023-06-08 Yeqing Lin , Mohammed AlQuraishi

Generating molecules that bind to specific proteins is an important but challenging task in drug discovery. Previous works usually generate atoms in an auto-regressive way, where element types and 3D coordinates of atoms are generated one…

Biomolecules · Quantitative Biology 2024-07-16 Haitao Lin , Yufei Huang , Odin Zhang , Siqi Ma , Meng Liu , Xuanjing Li , Lirong Wu , Jishui Wang , Tingjun Hou , Stan Z. Li

Proteins are dynamic molecular machines whose biological functions, spanning enzymatic catalysis, signal transduction, and structural adaptation, are intrinsically linked to their motions. Designing proteins with targeted dynamic…

Biomolecules · Quantitative Biology 2025-02-17 Bo Ni , Markus J. Buehler

Manifold learning techniques play a pivotal role in machine learning by revealing lower-dimensional embeddings within high-dimensional data, thus enhancing both the efficiency and interpretability of data analysis by transforming the data…

Neural and Evolutionary Computing · Computer Science 2025-05-02 Ben Cravens , Andrew Lensen , Paula Maddigan , Bing Xue

Protein structure prediction is pivotal for understanding the structure-function relationship of proteins, advancing biological research, and facilitating pharmaceutical development and experimental design. While deep learning methods and…

Machine Learning · Computer Science 2024-12-30 Kaihui Cheng , Ce Liu , Qingkun Su , Jun Wang , Liwei Zhang , Yining Tang , Yao Yao , Siyu Zhu , Yuan Qi

Construction of a scaffold structure that supports a desired motif, conferring protein function, shows promise for the design of vaccines and enzymes. But a general solution to this motif-scaffolding problem remains open. Current…

Biomolecules · Quantitative Biology 2023-03-21 Brian L. Trippe , Jason Yim , Doug Tischer , David Baker , Tamara Broderick , Regina Barzilay , Tommi Jaakkola

Deep learning is catalyzing a scientific revolution fueled by big data, accessible toolkits, and powerful computational resources, impacting many fields including protein structural modeling. Protein structural modeling, such as predicting…

Biomolecules · Quantitative Biology 2020-07-17 Wenhao Gao , Sai Pooja Mahajan , Jeremias Sulam , Jeffrey J. Gray

The de novo design of proteins refers to creating proteins with specific structures and functions that do not naturally exist. In recent years, the accumulation of high-quality protein structure and sequence data and technological…

Biomolecules · Quantitative Biology 2025-04-24 Yujie Qin , Ming He , Changyong Yu , Ming Ni , Xian Liu , Xiaochen Bo

Proteins are macromolecules that mediate a significant fraction of the cellular processes that underlie life. An important task in bioengineering is designing proteins with specific 3D structures and chemical properties which enable…

Quantitative Methods · Quantitative Biology 2022-05-31 Namrata Anand , Tudor Achim

The protein design problem involves finding polypeptide sequences folding into a given threedimensional structure. Its rigorous algorithmic solution is computationally demanding, involving a nested search in sequence and structure spaces.…

Quantum Physics · Physics 2024-07-11 Veronica Panizza , Philipp Hauke , Cristian Micheletti , Pietro Faccioli

Proteins are essential components of all living organisms and play a critical role in cellular survival. They have a broad range of applications, from clinical treatments to material engineering. This versatility has spurred the development…

Applications · Statistics 2025-03-28 Chenyu Ren , Daihai He , Jian Huang

Have you ever been troubled by the complexity and computational cost of SE(3) protein structure modeling and been amazed by the simplicity and power of language modeling? Recent work has shown promise in simplifying protein structures as…

Quantitative Methods · Quantitative Biology 2023-01-25 Zhangyang Gao , Cheng Tan , Stan Z. Li

Structure-based drug design has seen significant advancements with the integration of artificial intelligence (AI), particularly in the generation of hit and lead compounds. However, most AI-driven approaches neglect the importance of…

Machine Learning · Computer Science 2025-11-10 Xinheng He , Yijia Zhang , Haowei Lin , Xingang Peng , Xiangzhe Kong , Mingyu Li , Jianzhu Ma

Generating novel active molecules for a given protein is an extremely challenging task for generative models that requires an understanding of the complex physical interactions between the molecule and its environment. In this paper, we…