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Generative machine learning models are increasingly being used to design novel proteins for therapeutic and biotechnological applications. However, the current methods mostly focus on the design of proteins with a fixed backbone structure,…

Biomolecules · Quantitative Biology 2025-03-04 Petr Kouba , Joan Planas-Iglesias , Jiri Damborsky , Jiri Sedlar , Stanislav Mazurenko , Josef Sivic

Engineering new molecules with desirable functions and properties has the potential to extend our ability to engineer proteins beyond what nature has so far evolved. Advances in the so-called "de novo" design problem have recently been…

Machine Learning · Computer Science 2023-10-17 Adam Winnifrith , Carlos Outeiral , Brian Hie

Computational protein design is experiencing a transformation driven by AI/ML. However, the range of potential protein sequences and structures is astronomically vast, even for moderately sized proteins. Hence, achieving convergence between…

Distributed, Parallel, and Cluster Computing · Computer Science 2025-10-09 Aymen Alsaadi , Jonathan Ash , Mikhail Titov , Matteo Turilli , Andre Merzky , Shantenu Jha , Sagar Khare

Machine learning (ML) is becoming increasingly crucial in many fields of engineering but has not yet played out its full potential in bioprocess engineering. While experimentation has been accelerated by increasing levels of lab automation,…

In cancer therapeutics, protein-metal binding mechanisms critically govern the pharmacokinetics and targeting efficacy of drugs, thereby fundamentally shaping the rational design of anticancer metallodrugs. While conventional laboratory…

The impact of Transformer-based language models has been unprecedented in Natural Language Processing (NLP). The success of such models has also led to their adoption in other fields including bioinformatics. Taking this into account, this…

Machine Learning · Computer Science 2025-07-21 Nimisha Ghosh , Daniele Santoni , Debaleena Nawn , Eleonora Ottaviani , Giovanni Felici

This paper investigates the application of the transformer architecture in protein folding, as exemplified by DeepMind's AlphaFold project, and its implications for the understanding of so-called large language models. The prevailing…

Computers and Society · Computer Science 2024-12-10 Fabian Offert , Paul Kim , Qiaoyu Cai

Protein-RNA interactions are of vital importance to a variety of cellular activities. Both experimental and computational techniques have been developed to study the interactions. Due to the limitation of the previous database, especially…

Biomolecules · Quantitative Biology 2021-11-24 Junkang Wei , Siyuan Chen , Licheng Zong , Xin Gao , Yu Li

Designing de novo proteins beyond those found in nature holds significant promise for advancements in both scientific and engineering applications. Current methodologies for protein design often rely on AI-based models, such as surrogate…

Soft Condensed Matter · Physics 2024-02-08 A. Ghafarollahi , M. J. Buehler

Modern Protein Language Models (PLMs) apply transformer-based model architectures from natural language processing to biological sequences, predicting a variety of protein functions and properties. However, protein language has key…

Machine Learning · Computer Science 2026-02-25 Anna Hart , Chi Han , Jeonghwan Kim , Huimin Zhao , Heng Ji

The design of novel proteins has many applications but remains an attritional process with success in isolated cases. Meanwhile, deep learning technologies have exploded in popularity in recent years and are increasingly applicable to…

Biomolecules · Quantitative Biology 2018-11-07 Joe G Greener , Lewis Moffat , David T Jones

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

The protein folding problem has been fundamentally transformed by artificial intelligence, evolving from static structure prediction toward the modeling of dynamic conformational ensembles and complex biomolecular interactions. This review…

Computer Vision and Pattern Recognition · Computer Science 2026-03-20 Jingzhi Chen , Lijian Xu

We consider the protein sequence engineering problem, which aims to find protein sequences with high fitness levels, starting from a given wild-type sequence. Directed evolution has been a dominating paradigm in this field which has an…

Machine Learning · Computer Science 2025-01-20 Yinkai Wang , Jiaxing He , Yuanqi Du , Xiaohui Chen , Jianan Canal Li , Li-Ping Liu , Xiaolin Xu , Soha Hassoun

Protein dynamics underlie many biological functions, yet remain difficult to characterize due to the high computational cost of molecular dynamics simulations and the scarcity of dynamic structural data. This survey reviews recent advances…

Biomolecules · Quantitative Biology 2026-04-29 Haocheng Tang , Liang Shi , Ya-Shi Zhang , Xixian Liu , Jian Tang , Jiarui Lu

Representation learning and \emph{de novo} generation of proteins are pivotal computational biology tasks. Whilst natural language processing (NLP) techniques have proven highly effective for protein sequence modelling, structure modelling…

Quantitative Methods · Quantitative Biology 2025-01-08 Benoit Gaujac , Jérémie Donà , Liviu Copoiu , Timothy Atkinson , Thomas Pierrot , Thomas D. Barrett

Protein design has the potential to revolutionize biotechnology and medicine. While most efforts have focused on proteins with well-defined structures, increased recognition of the functional significance of intrinsically disordered…

Biomolecules · Quantitative Biology 2025-09-17 Giulio Tesei , Francesco Pesce , Kresten Lindorff-Larsen

Recent advances in Protein Language Models (PLMs) have transformed protein engineering, yet unlike their counterparts in Natural Language Processing (NLP), current PLMs exhibit a fundamental limitation: they excel in either Protein Language…

Computational Engineering, Finance, and Science · Computer Science 2025-09-16 Liuzhenghao Lv , Zongying Lin , Hao Li , Yuyang Liu , Jiaxi Cui , Calvin Yu-Chian Chen , Li Yuan , Yonghong Tian

Protein language models (PLMs) have shown promise in improving the understanding of protein sequences, contributing to advances in areas such as function prediction and protein engineering. However, training these models from scratch…

Machine Learning · Computer Science 2024-12-19 Shivasankaran Vanaja Pandi , Bharath Ramsundar

Computational methods for predicting and designing biomolecular structures are increasingly powerful. While previous approaches relied on physics-based modeling, modern tools, such as AlphaFold2 in CASP14, leverage artificial intelligence…

Biomolecules · Quantitative Biology 2025-11-05 Michael Chungyoun , Gabe Au , Britnie Carpentier , Sreevarsha Puvada , Courtney Thomas , Jeffrey J. Gray