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Large self-supervised models pretrained on millions of protein sequences have recently gained popularity in generating embeddings of protein sequences for protein function prediction. However, the absence of random baselines makes it…

Biomolecules · Quantitative Biology 2021-05-03 Tianyu Lu , Alex X. Lu , Alan M. Moses

Protein representation learning methods have shown great potential to yield useful representation for many downstream tasks, especially on protein classification. Moreover, a few recent studies have shown great promise in addressing…

Machine Learning · Computer Science 2023-04-11 Can Chen , Jingbo Zhou , Fan Wang , Xue Liu , Dejing Dou

Deciphering protein function remains a fundamental challenge in protein representation learning. The task presents significant difficulties for protein language models (PLMs) due to the sheer volume of functional annotation categories and…

Biomolecules · Quantitative Biology 2025-06-10 Zixuan Jiang , Renjing Xu

The Automated Protein Structure Analysis (APSA) method is used for the classification of supersecondary structures. Basis for the classification is the encoding of three-dimensional (3D) residue conformations into a 16-letter code (3D-1D…

Quantitative Methods · Quantitative Biology 2008-11-24 Sushilee Ranganathan , Dmitry Izotov , Elfi Kraka , Dieter Cremer

Deep learning has contributed to major advances in the prediction of protein structure from sequence, a fundamental problem in structural bioinformatics. With predictions now approaching the accuracy of crystallographic resolution in some…

Quantitative Methods · Quantitative Biology 2022-01-26 Mu Gao , Mark Coletti , Russell B. Davidson , Ryan Prout , Subil Abraham , Benjamin Hernandez , Ada Sedova

Attention-based models trained on protein sequences have demonstrated incredible success at classification and generation tasks relevant for artificial intelligence-driven protein design. However, we lack a sufficient understanding of how…

Machine Learning · Computer Science 2022-06-29 Erik Nijkamp , Jeffrey Ruffolo , Eli N. Weinstein , Nikhil Naik , Ali Madani

Machine learning is widely used to analyze biological sequence data. Non-sequential models such as SVMs or feed-forward neural networks are often used although they have no natural way of handling sequences of varying length. Recurrent…

Quantitative Methods · Quantitative Biology 2016-03-14 Søren Kaae Sønderby , Casper Kaae Sønderby , Henrik Nielsen , Ole Winther

Statistical analysis of evolutionary-related protein sequences provides insights about their structure, function, and history. We show that Restricted Boltzmann Machines (RBM), designed to learn complex high-dimensional data and their…

Quantitative Methods · Quantitative Biology 2019-02-28 Jérôme Tubiana , Simona Cocco , Rémi Monasson

Deep Learning (DL) algorithms hold great promise for applications in the field of computational biophysics. In fact, the vast amount of available molecular structures, as well as their notable complexity, constitutes an ideal context in…

Soft Condensed Matter · Physics 2019-01-07 Marco Giulini , Raffaello Potestio

How proteins fold remains a central unsolved problem in biology. While the idea of a folding code embedded in the amino acid sequence was introduced more than 6 decades ago, this code remains undefined. While we now have powerful predictive…

Biomolecules · Quantitative Biology 2025-11-04 Carlos Bustamante , Christian Kaiser , Erik Lindahl , Robert Sosa , Giovanni Volpe

Retrieving homologous protein sequences is essential for a broad range of protein modeling tasks such as fitness prediction, protein design, structure modeling, and protein-protein interactions. Traditional workflows have relied on a…

Quantitative Methods · Quantitative Biology 2025-06-11 Ruben Weitzman , Peter Mørch Groth , Lood Van Niekerk , Aoi Otani , Yarin Gal , Debora Marks , Pascal Notin

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

In this paper we address the problem of protein classification starting from a multi-view 2D representation of proteins. From each 3D protein structure, a large set of 2D projections is generated using the protein visualization software…

Computer Vision and Pattern Recognition · Computer Science 2019-10-30 Loris Nanni , Alessandra Lumini , Federica Pasquali , Sheryl Brahnam

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

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

Deep generative models that learn from the distribution of natural protein sequences and structures may enable the design of new proteins with valuable functions. While the majority of today's models focus on generating either sequences or…

Biomolecules · Quantitative Biology 2024-10-03 Chentong Wang , Sarah Alamdari , Carles Domingo-Enrich , Ava Amini , Kevin K. Yang

Protein sequences serve as a natural record of the evolutionary constraints that shape their functional structures. We show that it is possible to use only sequence information to go beyond predicting native structures and global stability…

Biomolecules · Quantitative Biology 2025-07-02 Ezequiel A. Galpern , Ernesto A. Roman , Diego U. Ferreiro

Proteins play a pivotal role in biological systems. The use of machine learning algorithms for protein classification can assist and even guide biological experiments, offering crucial insights for biotechnological applications. We…

Quantitative Methods · Quantitative Biology 2024-10-24 Yizheng Wang , Yixiao Zhai , Yijie Ding , Quan Zou

Automatic protein function prediction (AFP) is classified as a large-scale multi-label classification problem aimed at automating protein enrichment analysis to eliminate the current reliance on labor-intensive wet-lab methods. Currently,…

Quantitative Methods · Quantitative Biology 2023-07-26 Zihao Li , Changkun Jiang , Jianqiang Li

The protein backbone is described as a smooth curved and twisted line in three-dimensional (3D) space and characterized by its curvature $\kappa(s)$ and torsion $\tau(s)$ both expressed as a function of arc length s. It is shown that the…

Biomolecules · Quantitative Biology 2008-11-24 Sushilee Ranganathan , Dmitry Izotov , Elfi Kraka , Dieter Cremer