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The field of protein folding research has been greatly advanced by deep learning methods, with AlphaFold2 (AF2) demonstrating exceptional performance and atomic-level precision. As co-evolution is integral to protein structure prediction,…

Quantitative Methods · Quantitative Biology 2023-06-06 Le Zhang , Jiayang Chen , Tao Shen , Yu Li , Siqi Sun

Self-supervised neural language models with attention have recently been applied to biological sequence data, advancing structure, function and mutational effect prediction. Some protein language models, including MSA Transformer and…

Biomolecules · Quantitative Biology 2022-10-25 Umberto Lupo , Damiano Sgarbossa , Anne-Florence Bitbol

Computational models starting from large ensembles of evolutionarily related protein sequences capture a representation of protein families and learn constraints associated to protein structure and function. They thus open the possibility…

Biomolecules · Quantitative Biology 2024-12-30 Damiano Sgarbossa , Umberto Lupo , Anne-Florence Bitbol

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

The goal of protein representation learning is to extract knowledge from protein databases that can be applied to various protein-related downstream tasks. Although protein sequence, structure, and function are the three key modalities for…

Biomolecules · Quantitative Biology 2024-05-14 Eunji Ko , Seul Lee , Minseon Kim , Dongki Kim

Augmentation is an effective alternative to utilize the small amount of labeled protein data. However, most of the existing work focuses on design-ing new architectures or pre-training tasks, and relatively little work has studied data…

Quantitative Methods · Quantitative Biology 2024-03-05 Rui Sun , Lirong Wu , Haitao Lin , Yufei Huang , Stan Z. Li

In sequence-based predictions, conventionally an input sequence is represented by a multiple sequence alignment (MSA) or a representation derived from MSA, such as a position-specific scoring matrix. Recently, inspired by the development in…

Quantitative Methods · Quantitative Biology 2021-10-18 Nabil Ibtehaz , Daisuke Kihara

Protein sequence design, determined by amino acid sequences, are essential to protein engineering problems in drug discovery. Prior approaches have resorted to evolutionary strategies or Monte-Carlo methods for protein design, but often…

Multiple Sequence Alignment (MSA) plays a pivotal role in unveiling the evolutionary trajectories of protein families. The accuracy of protein structure predictions is often compromised for protein sequences that lack sufficient homologous…

Biomolecules · Quantitative Biology 2024-10-29 Bo Chen , Zhilei Bei , Xingyi Cheng , Pan Li , Jie Tang , Le Song

Understanding the relationships between protein sequence, structure and function is a long-standing biological challenge with manifold implications from drug design to our understanding of evolution. Recently, protein language models have…

Quantitative Methods · Quantitative Biology 2024-01-29 Dexiong Chen , Philip Hartout , Paolo Pellizzoni , Carlos Oliver , Karsten Borgwardt

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

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

Proteins are fundamental biological entities that play a key role in life activities. The amino acid sequences of proteins can be folded into stable 3D structures in the real physicochemical world, forming a special kind of…

Machine Learning · Computer Science 2023-01-04 Lirong Wu , Yufei Huang , Haitao Lin , Stan Z. Li

Predicting which proteins interact together from amino-acid sequences is an important task. We develop a method to pair interacting protein sequences which leverages the power of protein language models trained on multiple sequence…

Biomolecules · Quantitative Biology 2024-12-30 Umberto Lupo , Damiano Sgarbossa , Anne-Florence Bitbol

Protein structure prediction often hinges on multiple sequence alignments (MSAs), which underperform on low-homology and orphan proteins. We introduce PLAME, a lightweight MSA design framework that leverages evolutionary embeddings from…

Machine Learning · Computer Science 2025-09-29 Hanqun Cao , Xinyi Zhou , Zijun Gao , Chenyu Wang , Xin Gao , Zhi Zhang , Cesar de la Fuente-Nunez , Chunbin Gu , Ge Liu , Pheng-Ann Heng

We present the MSA-to-protein transformer, a generative model of protein sequences conditioned on protein families represented by multiple sequence alignments (MSAs). Unlike existing approaches to learning generative models of protein…

Biomolecules · Quantitative Biology 2022-04-05 Soumya Ram , Tristan Bepler

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

Protein language models (pLMs) produce per-residue representations that capture evolutionary and structural information, yet their mean-pooled sequence embeddings are not explicitly trained to reflect functional, evolutionary or structural…

Machine Learning · Computer Science 2026-05-11 Dan Ofer , Oriel Perets , Michal Linial , Nadav Rappoport

Geometric deep learning has recently achieved great success in non-Euclidean domains, and learning on 3D structures of large biomolecules is emerging as a distinct research area. However, its efficacy is largely constrained due to the…

Machine Learning · Computer Science 2023-10-31 Fang Wu , Lirong Wu , Dragomir Radev , Jinbo Xu , Stan Z. Li

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
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