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Inferring the structural properties of a protein from its amino acid sequence is a challenging yet important problem in biology. Structures are not known for the vast majority of protein sequences, but structure is critical for…

Machine Learning · Computer Science 2019-10-17 Tristan Bepler , Bonnie Berger

Adeno-associated viral (AAV) vectors are widely used delivery platforms in gene therapy, and the design of improved capsids is key to expanding their therapeutic potential. A central challenge in AAV bioengineering, as in protein design…

Predicting protein function from amino acid sequence remains a central challenge in data-scarce (low-$N$) regimes, limiting machine learning-guided protein design when only small amounts of assay-labeled sequence-function data are…

Machine Learning · Computer Science 2025-08-27 Darin Tsui , Kunal Talreja , Amirali Aghazadeh

Deep learning has transformed protein design, enabling accurate structure prediction, sequence optimization, and de novo protein generation. Advances in single-chain protein structure prediction via AlphaFold2, RoseTTAFold, ESMFold, and…

Machine Learning · Computer Science 2025-02-27 Gregory W. Kyro , Tianyin Qiu , Victor S. Batista

Proteins, essential to biological systems, perform functions intricately linked to their three-dimensional structures. Understanding the relationship between protein structures and their amino acid sequences remains a core challenge in…

Quantitative Methods · Quantitative Biology 2024-11-04 Liang He , Peiran Jin , Yaosen Min , Shufang Xie , Lijun Wu , Tao Qin , Xiaozhuan Liang , Kaiyuan Gao , Yuliang Jiang , Tie-Yan Liu

The capability of accurate prediction of protein functions and properties is essential in the biotechnology industry, e.g. drug development and artificial protein synthesis, etc. The main challenges of protein function prediction are the…

Quantitative Methods · Quantitative Biology 2021-12-02 Wei-Cheng Tseng , Po-Han Chi , Jia-Hua Wu , Min Sun

Proteins are essential to life's processes, underpinning evolution and diversity. Advances in sequencing technology have revealed millions of proteins, underscoring the need for sophisticated pre-trained protein models for biological…

Biomolecules · Quantitative Biology 2024-04-25 Shujian Jiao , Bingxuan Li , Lei Wang , Xiaojin Zhang , Wei Chen , Jiajie Peng , Zhongyu Wei

Pre-trained models have been successful in many protein engineering tasks. Most notably, sequence-based models have achieved state-of-the-art performance on protein fitness prediction while structure-based models have been used…

Machine Learning · Computer Science 2023-07-25 Antonia Boca , Simon Mathis

Adeno-associated viruses (AAVs) are promising vectors for gene therapy, but their native serotypes face limitations in tissue tropism, immune evasion, and production efficiency. Engineering capsids to overcome these hurdles is challenging…

Quantitative Methods · Quantitative Biology 2026-02-24 Mohammadreza Ghaffarzadeh-Esfahani , Yousof Gheisari

Learning effective protein representations is critical in a variety of tasks in biology such as predicting protein functions. Recent sequence representation learning methods based on Protein Language Models (PLMs) excel in sequence-based…

Quantitative Methods · Quantitative Biology 2023-10-19 Zuobai Zhang , Chuanrui Wang , Minghao Xu , Vijil Chenthamarakshan , Aurélie Lozano , Payel Das , Jian Tang

Recent advances in generative modeling show that pretrained representations can improve generation as conditioning features or alignment targets. Motivated by this, we study protein representations for predicting structures beyond…

Biomolecules · Quantitative Biology 2026-05-27 Taewon Kim , Hyosoon Jang , Hyunjin Seo , Seonghwan Seo , Hyeongwoo Kim , Wonho Zhung , Mingyeong Shin , Wooyoun Kim , Sungsoo Ahn

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

Deep learning has been widely used for protein engineering. However, it is limited by the lack of sufficient experimental data to train an accurate model for predicting the functional fitness of high-order mutants. Here, we develop SESNet,…

Quantitative Methods · Quantitative Biology 2023-04-10 Mingchen Li , Liqi Kang , Yi Xiong , Yu Guang Wang , Guisheng Fan , Pan Tan , Liang Hong

Deep learning has become a crucial tool in studying proteins. While the significance of modeling protein structure has been discussed extensively in the literature, amino acid types are typically included in the input as a default operation…

Quantitative Methods · Quantitative Biology 2024-07-01 Yang Tan , Lirong Zheng , Bozitao Zhong , Liang Hong , Bingxin Zhou

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…

In recent years, there has been a surge in the development of 3D structure-based pre-trained protein models, representing a significant advancement over pre-trained protein language models in various downstream tasks. However, most existing…

Machine Learning · Computer Science 2024-06-04 Jiale Zhao , Wanru Zhuang , Jia Song , Yaqi Li , Shuqi Lu

Amino acid sequence portrays most intrinsic form of a protein and expresses primary structure of protein. The order of amino acids in a sequence enables a protein to acquire a particular stable conformation that is responsible for the…

Machine Learning · Computer Science 2022-08-29 Ashish Ranjan , Md Shah Fahad , David Fernandez-Baca , Akshay Deepak , Sudhakar Tripathi

Machine Learning-guided solutions for protein learning tasks have made significant headway in recent years. However, success in scientific discovery tasks is limited by the accessibility of well-defined and labeled in-domain data. To tackle…

Machine Learning · Computer Science 2023-01-06 Ria Vinod , Pin-Yu Chen , Payel Das

Generative modeling has become a central paradigm in protein research, extending machine learning beyond structure prediction toward sequence design, backbone generation, inverse folding, and biomolecular interaction modeling. However, the…

Machine Learning · Computer Science 2026-03-30 Senura Hansaja Wanasekara , Minh-Duong Nguyen , Xiaochen Liu , Nguyen H. Tran , Ken-Tye Yong

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
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