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Predicting the fitness impact of mutations is central to protein engineering but constrained by limited assays relative to the size of sequence space. Protein language models (pLMs) trained with masked language modeling (MLM) exhibit strong…

Machine Learning · Computer Science 2026-04-14 Jigang Fan , Xiaoran Jiao , Shengdong Lin , Zhanming Liang , Weian Mao , Chenchen Jing , Hao Chen , Chunhua Shen

Motivation: Site directed mutagenesis is widely used to understand the structure and function of biomolecules. Computational prediction of protein mutation impacts offers a fast, economical and potentially accurate alternative to laboratory…

Quantitative Methods · Quantitative Biology 2017-04-03 Zixuan Cang , Guo-Wei Wei

Structure-informed protein representation learning is essential for effective protein function annotation and \textit{de novo} design. However, the presence of inherent noise in both crystal and AlphaFold-predicted structures poses…

Biomolecules · Quantitative Biology 2025-03-25 Zhongyue Zhang , Runze Ma , Yanjie Huang , Shuangjia Zheng

Proteins perform much of the work in living organisms, and consequently the development of efficient computational methods for protein representation is essential for advancing large-scale biological research. Most current approaches…

Quantitative Methods · Quantitative Biology 2023-06-09 Francesco Ceccarelli , Lorenzo Giusti , Sean B. Holden , Pietro Liò

Predicting the docking between proteins and ligands is a crucial and challenging task for drug discovery. However, traditional docking methods mainly rely on scoring functions, and deep learning-based docking approaches usually neglect the…

Biomolecules · Quantitative Biology 2026-01-06 Yiqiang Yi , Xu Wan , Yatao Bian , Le Ou-Yang , Peilin Zhao

Large-scale Protein Language Models (PLMs) have improved performance in protein prediction tasks, ranging from 3D structure prediction to various function predictions. In particular, AlphaFold, a ground-breaking AI system, could potentially…

Quantitative Methods · Quantitative Biology 2022-10-18 Mingyang Hu , Fajie Yuan , Kevin K. Yang , Fusong Ju , Jin Su , Hui Wang , Fei Yang , Qiuyang Ding

Fine-tuning pre-trained language models, particularly large language models, demands extensive computing resources and can result in varying performance outcomes across different domains and datasets. This paper examines the approach of…

Computation and Language · Computer Science 2024-06-19 Guodong Du , Jing Li , Hanting Liu , Runhua Jiang , Shuyang Yu , Yifei Guo , Sim Kuan Goh , Ho-Kin Tang

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

Proteins are macromolecules that perform essential functions in all living organisms. Designing novel proteins with specific structures and desired functions has been a long-standing challenge in the field of bioengineering. Existing…

Biomolecules · Quantitative Biology 2023-03-03 Chence Shi , Chuanrui Wang , Jiarui Lu , Bozitao Zhong , Jian Tang

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

Protein representation learning is critical for numerous biological tasks. Recently, large transformer-based protein language models (pLMs) pretrained on large scale protein sequences have demonstrated significant success in sequence-based…

Machine Learning · Computer Science 2025-08-12 Xuefeng Liu , Songhao Jiang , Chih-chan Tien , Jinbo Xu , Rick Stevens

Proteins have evolved through mutations, amino acid substitutions, since life appeared on Earth, some 109 years ago. The study of these phenomena has been of particular significance because of their impact on protein stability, function,…

Biomolecules · Quantitative Biology 2023-10-25 Jorge A. Vila

Information networks are ubiquitous and are ideal for modeling relational data. Networks being sparse and irregular, network embedding algorithms have caught the attention of many researchers, who came up with numerous embeddings algorithms…

Machine Learning · Computer Science 2020-09-25 Junshan Wang , Yilun Jin , Guojie Song , Xiaojun Ma

Variational auto-encoder frameworks have demonstrated success in reducing complex nonlinear dynamics in molecular simulation to a single non-linear embedding. In this work, we illustrate how this non-linear latent embedding can be used as a…

Machine Learning · Statistics 2018-01-03 Mohammad M. Sultan , Hannah K. Wayment-Steele , Vijay S. Pande

Structural design of neural networks is crucial for the success of deep learning. While most prior works in evolutionary learning aim at directly searching the structure of a network, few attempts have been made on another promising track,…

Computer Vision and Pattern Recognition · Computer Science 2022-08-05 Yuchen Liu , S. Y. Kung , David Wentzlaff

The advent of highly accurate protein structure prediction methods has fueled an exponential expansion of the protein structure database. Consequently, there is a rising demand for rapid and precise structural homolog search. Traditional…

Biomolecules · Quantitative Biology 2023-12-01 Yuan Liu , Hong-Bin Shen

Understanding protein structure-function relationships is a key challenge in computational biology, with applications across the biotechnology and pharmaceutical industries. While it is known that protein structure directly impacts protein…

Biomolecules · Quantitative Biology 2020-11-02 Nicolas Swenson , Aditi S. Krishnapriyan , Aydin Buluc , Dmitriy Morozov , Katherine Yelick

Proteins are the basic building blocks of life. They usually perform functions by folding to a particular structure. Understanding the folding process could help the researchers to understand the functions of proteins and could also help to…

Computational Engineering, Finance, and Science · Computer Science 2015-10-21 Jianzhu Ma

Understanding protein sequences is vital and urgent for biology, healthcare, and medicine. Labeling approaches are expensive yet time-consuming, while the amount of unlabeled data is increasing quite faster than that of the labeled data due…

Computation and Language · Computer Science 2021-11-01 Liang He , Shizhuo Zhang , Lijun Wu , Huanhuan Xia , Fusong Ju , He Zhang , Siyuan Liu , Yingce Xia , Jianwei Zhu , Pan Deng , Bin Shao , Tao Qin , Tie-Yan Liu

Fine-tuning Pre-trained protein language models (PLMs) has emerged as a prominent strategy for enhancing downstream prediction tasks, often outperforming traditional supervised learning approaches. As a widely applied powerful technique in…

Computation and Language · Computer Science 2024-04-24 Yang Tan , Mingchen Li , Bingxin Zhou , Bozitao Zhong , Lirong Zheng , Pan Tan , Ziyi Zhou , Huiqun Yu , Guisheng Fan , Liang Hong