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While DeepMind has tentatively solved protein folding, its inverse problem -- protein design which predicts protein sequences from their 3D structures -- still faces significant challenges. Particularly, the lack of large-scale standardized…

Quantitative Methods · Quantitative Biology 2022-02-15 Zhangyang Gao , Cheng Tan , Stan Z. Li

Proteins perform critical processes in all living systems: converting solar energy into chemical energy, replicating DNA, as the basis of highly performant materials, sensing and much more. While an incredible range of functionality has…

Biomolecules · Quantitative Biology 2021-09-29 Leonardo V. Castorina , Rokas Petrenas , Kartic Subr , Christopher W. Wood

Protein folding models have achieved groundbreaking results typically via a combination of integrating domain knowledge into the architectural blocks and training pipelines. Nonetheless, given the success of generative models across…

Machine Learning · Computer Science 2025-12-11 Yuyang Wang , Jiarui Lu , Navdeep Jaitly , Josh Susskind , Miguel Angel Bautista

Inverse protein folding, the process of designing sequences that fold into a specific 3D structure, is crucial in bio-engineering and drug discovery. Traditional methods rely on experimentally resolved structures, but these cover only a…

Biomolecules · Quantitative Biology 2023-11-27 Igor Melnyk , Aurelie Lozano , Payel Das , Vijil Chenthamarakshan

Proteins exist as a dynamic ensemble of multiple conformations, and these motions are often crucial for their functions. However, current structure prediction methods predominantly yield a single conformation, overlooking the conformational…

Biomolecules · Quantitative Biology 2025-06-18 Advaith Maddipatla , Nadav Bojan Sellam , Meital Bojan , Sanketh Vedula , Paul Schanda , Ailie Marx , Alex M. Bronstein

Recent years have witnessed a surge in the development of protein foundation models, significantly improving performance in protein prediction and generative tasks ranging from 3D structure prediction and protein design to conformational…

Quantitative Methods · Quantitative Biology 2024-10-08 Fei Ye , Zaixiang Zheng , Dongyu Xue , Yuning Shen , Lihao Wang , Yiming Ma , Yan Wang , Xinyou Wang , Xiangxin Zhou , Quanquan Gu

The remarkable success of AlphaFold2 in providing accurate atomic-level prediction of protein structures from their amino acid sequence has transformed approaches to the protein folding problem. However, its core paradigm of mapping one…

Applications · Statistics 2025-12-12 Yongkai Chen , Samuel WK Wong , SC Kou

Protein structures and functions are determined by a contiguous arrangement of amino acid sequences. Designing novel protein sequences and structures with desired geometry and functions is a complex task with large state spaces. Here we…

Chemical Physics · Physics 2022-09-01 Xeerak Agha , Nihang Fu , Jianjun Hu

Deep learning has made significant progress in protein structure prediction, advancing the development of computational biology. However, despite the high accuracy achieved in predicting single-chain structures, a significant number of…

Biomolecules · Quantitative Biology 2024-03-08 Zhaoqun Li , Jingcheng Yu , Qiwei Ye

Deep learning has transformed protein design, enabling accurate structure prediction, sequence optimization, and de novo protein generation. Advances in single-chain protein structure prediction via AlphaFold2, RoseTTAFold, ESMFold, and…

Machine Learning · Computer Science 2025-02-27 Gregory W. Kyro , Tianyin Qiu , Victor S. Batista

Despite considerable progress, ab initio protein structure prediction remains suboptimal. A crowdsourcing approach is the online puzzle video game Foldit, that provided several useful results that matched or even outperformed…

Biomolecules · Quantitative Biology 2020-11-09 Dimitra N. Panou , Martin Reczko

The protein design problem involves finding polypeptide sequences folding into a given threedimensional structure. Its rigorous algorithmic solution is computationally demanding, involving a nested search in sequence and structure spaces.…

Quantum Physics · Physics 2024-07-11 Veronica Panizza , Philipp Hauke , Cristian Micheletti , Pietro Faccioli

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

Recent advances in Artificial Intelligence have enabled multi-modal systems to model and translate diverse information spaces. Extending beyond text and vision, we introduce OneProt, a multi-modal AI for proteins that integrates structural,…

The recent breakthrough of AlphaFold3 in modeling complex biomolecular interactions, including those between proteins and ligands, nucleotides, or metal ions, creates new opportunities for protein design. In so-called inverse protein…

Biomolecules · Quantitative Biology 2025-07-22 Kai Yi , Kiarash Jamali , Sjors H. W. Scheres

The diverse nature of protein prediction tasks has traditionally necessitated specialized models, hindering the development of broadly applicable and computationally efficient Protein Language Models (PLMs). In this work, we introduce…

The goal of Protein Structure Prediction (PSP) problem is to predict a protein's 3D structure (confirmation) from its amino acid sequence. The problem has been a 'holy grail' of science since the Noble prize-winning work of Anfinsen…

Biomolecules · Quantitative Biology 2023-01-24 Abbi Abdel-Rehim , Oghenejokpeme Orhobor , Hang Lou , Hao Ni , Ross D. King

Generative modeling has become a central paradigm in protein research, extending machine learning beyond structure prediction toward sequence design, backbone generation, inverse folding, and biomolecular interaction modeling. However, the…

Machine Learning · Computer Science 2026-03-30 Senura Hansaja Wanasekara , Minh-Duong Nguyen , Xiaochen Liu , Nguyen H. Tran , Ken-Tye Yong

Disordered proteins play essential roles in myriad cellular processes, yet their structural characterization remains a major challenge due to their dynamic and heterogeneous nature. We here present a community-driven initiative to address…

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
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