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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

Computational protein design aims at constructing novel or improved functions on the structure of a given protein backbone and has important applications in the pharmaceutical and biotechnical industry. The underlying combinatorial…

Data Structures and Algorithms · Computer Science 2011-03-29 Stefan Canzar , Nora C. Toussaint , Gunnar W. Klau

We introduce AMix-1, a powerful protein foundation model built on Bayesian Flow Networks and empowered by a systematic training methodology, encompassing pretraining scaling laws, emergent capability analysis, in-context learning mechanism,…

This paper presents a novel generative model for Computer Aided Design (CAD) that 1) represents high-level design concepts of a CAD model as a three-level hierarchical tree of neural codes, from global part arrangement down to local curve…

Computer Vision and Pattern Recognition · Computer Science 2023-07-04 Xiang Xu , Pradeep Kumar Jayaraman , Joseph G. Lambourne , Karl D. D. Willis , Yasutaka Furukawa

Computational protein design has a wide variety of applications. Despite its remarkable success, designing a protein for a given structure and function is still a challenging task. On the other hand, the number of solved protein structures…

Quantitative Methods · Quantitative Biology 2018-04-26 Jingxue Wang , Huali Cao , John Z. H. Zhang , Yifei Qi

We propose a new and effective means for designing stable and fast-folding polypeptide sequences using a cumulant expansion of the molecular partition function. This method is unique in that $T_{Z}$, the ``cumulant design temperature''…

Condensed Matter · Physics 2007-05-23 Michael P. Morrissey , Eugene I. Shakhnovich

The design of novel protein sequences with targeted functionalities underpins a central theme in protein engineering, impacting diverse fields such as drug discovery and enzymatic engineering. However, navigating this vast combinatorial…

Biomolecules · Quantitative Biology 2024-02-19 Yiheng Zhu , Zitai Kong , Jialu Wu , Weize Liu , Yuqiang Han , Mingze Yin , Hongxia Xu , Chang-Yu Hsieh , Tingjun Hou

Inverse protein folding, the process of designing sequences that fold into a specific 3D structure, is crucial in bio-engineering and drug discovery. Traditional methods rely on experimentally resolved structures, but these cover only a…

Biomolecules · Quantitative Biology 2023-11-27 Igor Melnyk , Aurelie Lozano , Payel Das , Vijil Chenthamarakshan

In nature the three-dimensional structure of a protein is encoded in the corresponding gene. In this paper we describe a new method for encoding the three-dimensional structure of a protein into a binary sequence. The feature of the method…

Combinatorics · Mathematics 2007-05-23 Naoto Morikawa

Knowledge of a protein's atomic conformational ensemble is critical to determining its function, yet state-of-the-art ensemble prediction models are limited by lack of high-quality conformational data from simulation or experiment. Recent…

Machine Learning · Computer Science 2026-05-12 Jay Shenoy , Miro Astore , Axel Levy , Frédéric Poitevin , Sonya M. Hanson , Gordon Wetzstein

Recently, deep learning has made rapid progress in antibody design, which plays a key role in the advancement of therapeutics. A dominant paradigm is to train a model to jointly generate the antibody sequence and the structure as a…

Quantitative Methods · Quantitative Biology 2025-01-20 Nayoung Kim , Minsu Kim , Sungsoo Ahn , Jinkyoo Park

In this study, we propose an analytic statistical mechanics approach to solve a fundamental problem in biological physics called protein design. Protein design is an inverse problem of protein structure prediction, and its solution is the…

Statistical Mechanics · Physics 2022-10-26 Tomoei Takahashi , George Chikenji , Kei Tokita

Exploring and understanding the protein-folding problem has been a long-standing challenge in molecular biology. Here, using molecular dynamics simulation, we reveal how parallel distributed adjacent planar peptide groups of unfolded…

Biomolecules · Quantitative Biology 2019-01-11 Xiaoliang Ma , Chengyu Hou , Liping Shi , Long Li , Jiacheng Li , Lin Ye , Lin Yang , Xiaodong He

We present Hecate, a modular lossless genomic compression framework. It is designed around uncommon but practical source-coding choices. Unlike many single-method compressors, Hecate treats compression as a conditional coding problem over…

Data Structures and Algorithms · Computer Science 2026-03-17 Kamila Szewczyk , Sven Rahmann

Representation learning for protein biochemical space faces a difficult trade-off: protein language models excel at capturing long-range biological semantics but often miss fine-grained chemical details. Conversely, chemical language models…

Biomolecules · Quantitative Biology 2026-03-03 Chunbin Gu , Zijun Gao , Mutian He , Jingjie Zhang , Haipeng Wen , Zihao Luo , Xiaorui Wang , Hanqun Cao , Jiajun Bu , Chang-Yu Hsieh , Pheng Ann Heng

Computational protein design facilitates discovery of novel proteins with prescribed structure and functionality. Exciting designs were recently reported using novel data-driven methodologies that can be roughly divided into two categories:…

Biological Physics · Physics 2023-03-28 Cyril Malbranke , David Bikard , Simona Cocco , Rémi Monasson , Jérôme Tubiana

Proteins are inherently multiscale physical systems whose functional properties emerge from coordinated structural organization across multiple spatial resolutions, ranging from atomic interactions to global fold topology. However, existing…

Machine Learning · Computer Science 2026-05-13 Viet Thanh Duy Nguyen , John K. Johnstone , Truong-Son Hy

Cryogenic electron microscopy (cryo-EM) provides a unique opportunity to study the structural heterogeneity of biomolecules. Being able to explain this heterogeneity with atomic models would help our understanding of their functional…

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

Generative models for structure-based drug design are often limited to a specific modality, restricting their broader applicability. To address this challenge, we introduce FuncBind, a framework based on computer vision to generate…

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