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Protein language models (PLMs) learn probability distributions over natural protein sequences. By learning from hundreds of millions of natural protein sequences, protein understanding and design capabilities emerge. Recent works have shown…

Quantitative Methods · Quantitative Biology 2026-02-27 Timothy Fei Truong , Tristan Bepler

Proteins are essential macromolecules defined by their amino acid sequences, which determine their three-dimensional structures and, consequently, their functions in all living organisms. Therefore, generative protein modeling necessitates…

Machine Learning · Computer Science 2024-10-18 Xinyou Wang , Zaixiang Zheng , Fei Ye , Dongyu Xue , Shujian Huang , Quanquan Gu

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

Numerous cellular functions rely on protein$\unicode{x2013}$protein interactions. Efforts to comprehensively characterize them remain challenged however by the diversity of molecular recognition mechanisms employed within the proteome. Deep…

Biomolecules · Quantitative Biology 2023-12-08 Julia R. Rogers , Gergő Nikolényi , Mohammed AlQuraishi

Masked language modeling (MLM) is the standard objective for training protein language models, typically implemented by randomly masking individual residues at a fixed rate (e.g., 15%). This practice implicitly assumes that all sequence…

Machine Learning · Computer Science 2026-05-19 Thomas Walton , Ayan Goel , Amirali Aghazadeh

With the exponential increase of the protein sequence databases over time, multiple-sequence alignment (MSA) methods, like PSI-BLAST, perform exhaustive and time-consuming database search to retrieve evolutionary information. The resulting…

Quantitative Methods · Quantitative Biology 2023-08-21 Issar Arab

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

Protein-protein interactions (PPIs) are essentials for many biological processes where two or more proteins physically bind together to achieve their functions. Modeling PPIs is useful for many biomedical applications, such as vaccine…

Biomolecules · Quantitative Biology 2021-12-10 Yang Xue , Zijing Liu , Xiaomin Fang , Fan Wang

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

The local structure of a protein strongly impacts its function and interactions with other molecules. Therefore, a concise, informative representation of a local protein environment is essential for modeling and designing proteins and…

Protein language models (PLMs) learn contextual representations from protein sequences and are profoundly impacting various scientific disciplines spanning protein design, drug discovery, and structural predictions. One particular research…

Quantitative Methods · Quantitative Biology 2024-02-07 Andreas Dounas , Tudor-Stefan Cotet , Alexander Yermanos

Structure determination is key to understanding protein function at a molecular level. Whilst significant advances have been made in predicting structure and function from amino acid sequence, researchers must still rely on expensive,…

Computer Vision and Pattern Recognition · Computer Science 2020-09-01 Alexander Hudson , Shaogang Gong

Recent advancements in machine learning (ML) are transforming the field of structural biology. For example, AlphaFold, a groundbreaking neural network for protein structure prediction, has been widely adopted by researchers. The…

While protein language models (PLMs) are one of the most promising avenues of research for future de novo protein design, the way in which they transform sequences to hidden representations, as well as the information encoded in such…

Machine Learning · Computer Science 2026-05-29 Kosio Beshkov , Anders Malthe-Sørenssen

Determining the different conformational states of a protein and the transition paths between them is key to fully understanding the relationship between biomolecular structure and function. This can be accomplished by sampling protein…

Biological Physics · Physics 2021-03-24 Venkata K. Ramaswamy , Chris G. Willcocks , Matteo T. Degiacomi

Accurately predicting protein melting temperature changes (Delta Tm) is fundamental for assessing protein stability and guiding protein engineering. Leveraging multi-modal protein representations has shown great promise in capturing the…

Machine Learning · Computer Science 2025-03-25 Daiheng Zhang , Yan Zeng , Xinyu Hong , Jinbo Xu

Accurate extraction of molecular representations is a critical step in the drug discovery process. In recent years, significant progress has been made in molecular representation learning methods, among which multi-modal molecular…

Machine Learning · Computer Science 2025-05-13 Rong Yin , Ruyue Liu , Xiaoshuai Hao , Xingrui Zhou , Yong Liu , Can Ma , Weiping Wang

Accurate protein function prediction requires integrating heterogeneous intrinsic signals (e.g., sequence and structure) with noisy extrinsic contexts (e.g., protein-protein interactions and GO term annotations). However, two key challenges…

Machine Learning · Computer Science 2025-10-28 Runjie Zheng , Zhen Wang , Anjie Qiao , Jiancong Xie , Jiahua Rao , Yuedong Yang

Proteins are responsible for the most diverse set of functions in biology. The ability to extract information from protein sequences and to predict the effects of mutations is extremely valuable in many domains of biology and medicine.…

Quantitative Methods · Quantitative Biology 2018-01-04 Sam Sinai , Eric Kelsic , George M. Church , Martin A. Nowak

Machine learning models of vastly different modalities and architectures are being trained to predict the behavior of molecules, materials, and proteins. However, it remains unclear whether they learn similar internal representations of…

Machine Learning · Computer Science 2025-12-04 Sathya Edamadaka , Soojung Yang , Ju Li , Rafael Gómez-Bombarelli