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Directed evolution of proteins has been the most effective method for protein engineering. However, a new paradigm is emerging, fusing the library generation and screening approaches of traditional directed evolution with computation…

Biomolecules · Quantitative Biology 2023-05-29 Kadina E. Johnston , Clara Fannjiang , Bruce J. Wittmann , Brian L. Hie , Kevin K. Yang , Zachary Wu

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

To reduce experimental effort associated with directed protein evolution and to explore the sequence space encoded by mutating multiple positions simultaneously, we incorporate machine learning in the directed evolution workflow.…

Biomolecules · Quantitative Biology 2020-01-07 Zachary Wu , S. B. Jennifer Kan , Russell D. Lewis , Bruce J. Wittmann , Frances H. Arnold

Protein sequence design is a challenging problem in protein engineering, which aims to discover novel proteins with useful biological functions. Directed evolution is a widely-used approach for protein sequence design, which mimics the…

Machine Learning · Computer Science 2023-03-21 Chuanjiao Zong

Machine learning (ML)-guided directed evolution is a new paradigm for biological design that enables optimization of complex functions. ML methods use data to predict how sequence maps to function without requiring a detailed model of the…

Biomolecules · Quantitative Biology 2019-04-23 Kevin K. Yang , Zachary Wu , Frances H. Arnold

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

Directed evolution is a molecular biology technique that is transforming protein engineering by creating proteins with desirable properties and functions. However, it is experimentally impossible to perform the deep mutational scanning of…

Biomolecules · Quantitative Biology 2023-06-09 Yuchi Qiu , Guo-Wei Wei

Enzyme is the major workhorse to carry out the diverse cellular functions. It catalyzes the biological reactions with a high specificity, with its topology playing a crucial role. For ecologically safe production of numerous bioproducts…

Biomolecules · Quantitative Biology 2021-06-04 Prabha Sankara Narayanan , Ashish Runthala

Protein evolution through amino acid mutations is a cornerstone of life sciences. Recent advances in protein language models have shown rich evolutionary patterns, offering unprecedented potential for in-silicon directed evolution. However,…

Artificial Intelligence · Computer Science 2026-01-08 Yaodong Yang , Yang Wang , Jinpeng Li , Pei Guo , Da Han , Guangyong Chen , Pheng-Ann Heng

Directed evolution plays an indispensable role in protein engineering that revises existing protein sequences to attain new or enhanced functions. Accurately predicting the effects of protein variants necessitates an in-depth understanding…

Quantitative Methods · Quantitative Biology 2023-06-09 Yang Tan , Bingxin Zhou , Yuanhong Jiang , Yu Guang Wang , Liang Hong

While modern biotechnologies allow synthesizing new proteins and function measurements at scale, efficiently exploring a protein sequence space and engineering it remains a daunting task due to the vast sequence space of any given protein.…

Biomolecules · Quantitative Biology 2024-01-15 Jiahao Qiu , Hui Yuan , Jinghong Zhang , Wentao Chen , Huazheng Wang , Mengdi Wang

DNA and other biopolymers are being investigated as new computing substrates and alternative to silicon-based digital computers. However, the established top-down design of biomolecular interaction networks remains challenging and does not…

Soft Condensed Matter · Physics 2025-11-19 Tanmay Pandey , Petro Feketa , Jan Steinkühler

We consider the protein sequence engineering problem, which aims to find protein sequences with high fitness levels, starting from a given wild-type sequence. Directed evolution has been a dominating paradigm in this field which has an…

Machine Learning · Computer Science 2025-01-20 Yinkai Wang , Jiaxing He , Yuanqi Du , Xiaohui Chen , Jianan Canal Li , Li-Ping Liu , Xiaolin Xu , Soha Hassoun

Directed evolution as a widely-used engineering strategy faces obstacles in finding desired mutants from the massive size of candidate modifications. While deep learning methods learn protein contexts to establish feasible searching space,…

Quantitative Methods · Quantitative Biology 2023-04-18 Bingxin Zhou , Outongyi Lv , Kai Yi , Xinye Xiong , Pan Tan , Liang Hong , Yu Guang Wang

Protein fitness optimization involves finding a protein sequence that maximizes desired quantitative properties in a combinatorially large design space of possible sequences. Recent advances in steering protein generative models (e.g.,…

Biomolecules · Quantitative Biology 2025-10-22 Jason Yang , Wenda Chu , Daniel Khalil , Raul Astudillo , Bruce J. Wittmann , Frances H. Arnold , Yisong Yue

Data-efficient image classification is a challenging task that aims to solve image classification using small training data. Neural network-based deep learning methods are effective for image classification, but they typically require…

Neural and Evolutionary Computing · Computer Science 2022-12-05 Ying Bi , Bing Xue , Mengjie Zhang

Protein engineering seeks to identify protein sequences with optimized properties. When guided by machine learning, protein sequence generation methods can draw on prior knowledge and experimental efforts to improve this process. In this…

Quantitative Methods · Quantitative Biology 2021-05-28 Zachary Wu , Kadina E. Johnston , Frances H. Arnold , Kevin K. Yang

Inverse protein folding -- the task of predicting a protein sequence from its backbone atom coordinates -- has surfaced as an important problem in the "top down", de novo design of proteins. Contemporary approaches have cast this problem as…

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

Motivation: Protein embedding, which represents proteins as numerical vectors, is a crucial step in various learning-based protein annotation/classification problems, including gene ontology prediction, protein-protein interaction…

Genomics · Quantitative Biology 2024-05-21 Jiayu Shang , Cheng Peng , Yongxin Ji , Jiaojiao Guan , Dehan Cai , Xubo Tang , Yanni Sun
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