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Inverse protein folding generates valid amino acid sequences that can fold into a desired protein structure, with recent deep-learning advances showing strong potential and competitive performance. However, challenges remain, such as…

Biomolecules · Quantitative Biology 2025-07-29 Peizhen Bai , Filip Miljković , Xianyuan Liu , Leonardo De Maria , Rebecca Croasdale-Wood , Owen Rackham , Haiping Lu

AI-assisted protein design has emerged as a critical tool for advancing biotechnology, as deep generative models have demonstrated their reliability in this domain. However, most existing models primarily utilize protein sequence or…

Computational Engineering, Finance, and Science · Computer Science 2026-05-27 Changjian Zhou , Yuexi Qiu , Jia Song

The prediction of protein stability changes following single-point mutations plays a pivotal role in computational biology, particularly in areas like drug discovery, enzyme reengineering, and genetic disease analysis. Although…

Quantitative Methods · Quantitative Biology 2025-05-01 Ivan Rossi , Guido Barducci , Tiziana Sanavia , Paola Turina , Emidio Capriotti , Piero Fariselli

Protein inverse folding aims to identify viable amino acid sequences that can fold into given protein structures, enabling the design of novel proteins with desired functions for applications in drug discovery, enzyme engineering, and…

Quantitative Methods · Quantitative Biology 2024-11-05 Taoyu Wu , Yu Guang Wang , Yiqing Shen

Construction of a scaffold structure that supports a desired motif, conferring protein function, shows promise for the design of vaccines and enzymes. But a general solution to this motif-scaffolding problem remains open. Current…

Biomolecules · Quantitative Biology 2023-03-21 Brian L. Trippe , Jason Yim , Doug Tischer , David Baker , Tamara Broderick , Regina Barzilay , Tommi Jaakkola

Protein inverse folding aims to design an amino acid sequence that will fold into a given backbone structure, serving as a central task in protein design. Two main paradigms have been widely explored. Template-based methods exploit…

Machine Learning · Computer Science 2026-03-17 Yiran Zhu , Changxi Chi , Hongxin Xiang , Wenjie Du , Xiaoqi Wang , Jun Xia

To understand the black-box characteristics of deep networks, counterfactual explanation that deduces not only the important features of an input space but also how those features should be modified to classify input as a target class has…

Machine Learning · Computer Science 2022-08-15 Hong-Gyu Jung , Sin-Han Kang , Hee-Dong Kim , Dong-Ok Won , Seong-Whan Lee

Protein structure prediction is a critical and longstanding challenge in biology, garnering widespread interest due to its significance in understanding biological processes. A particular area of focus is the prediction of missing loops in…

Proteins are complex biomolecules that perform a variety of crucial functions within living organisms. Designing and generating novel proteins can pave the way for many future synthetic biology applications, including drug discovery.…

Artificial intelligence is increasingly leveraged across various domains to automate decision-making processes that significantly impact human lives. In medical image analysis, deep learning models have demonstrated remarkable performance.…

Machine Learning · Computer Science 2025-07-28 Julia Siekiera , Stefan Kramer

Directed evolution as a widely-used engineering strategy faces obstacles in finding desired mutants from the massive size of candidate modifications. While deep learning methods learn protein contexts to establish feasible searching space,…

Quantitative Methods · Quantitative Biology 2023-04-18 Bingxin Zhou , Outongyi Lv , Kai Yi , Xinye Xiong , Pan Tan , Liang Hong , Yu Guang Wang

The inapplicability of amino acid covariation methods to small protein families has limited their use for structural annotation of whole genomes. Recently, deep learning has shown promise in allowing accurate residue-residue contact…

Biomolecules · Quantitative Biology 2019-09-10 Joe G Greener , Shaun M Kandathil , David T Jones

Proteins are miniature machines whose function depends on their three-dimensional (3D) structure. Determining this structure computationally remains an unsolved grand challenge. A major bottleneck involves selecting the most accurate…

Quantitative Methods · Quantitative Biology 2020-11-30 Stephan Eismann , Patricia Suriana , Bowen Jing , Raphael J. L. Townshend , Ron O. Dror

Computational protein design (CPD) refers to the use of computational methods to design proteins. Traditional methods relying on energy functions and heuristic algorithms for sequence design are inefficient and do not meet the demands of…

Machine Learning · Computer Science 2024-10-30 Xiaoqi Ling , Cheng Cai , Demin Kong , Zhisheng Wei , Jing Wu , Lei Wang , Zhaohong Deng

Coarse-grained (CG) molecular dynamics simulations enable efficient exploration of protein conformational ensembles. However, reconstructing atomic details from CG structures (backmapping) remains a challenging problem. Current approaches…

Machine Learning · Computer Science 2025-12-30 Xu Han , Yuancheng Sun , Kai Chen , Yuxuan Ren , Kang Liu , Qiwei Ye

Counterfactual instances are a powerful tool to obtain valuable insights into automated decision processes, describing the necessary minimal changes in the input space to alter the prediction towards a desired target. Most previous…

Machine Learning · Computer Science 2021-06-07 Robert-Florian Samoilescu , Arnaud Van Looveren , Janis Klaise

Accurately modeling the protein fitness landscapes holds great importance for protein engineering. Recently, due to their capacity and representation ability, pre-trained protein language models have achieved state-of-the-art performance in…

Biomolecules · Quantitative Biology 2024-02-06 Ziyi Zhou , Liang Zhang , Yuanxi Yu , Mingchen Li , Liang Hong , Pan Tan

A core challenge in structural biophysics is generating biomolecular conformations that are both physically plausible and consistent with experimental measurements. While sequence-to-structure diffusion models provide powerful priors,…

Machine Learning · Computer Science 2026-05-15 Minhuan Li , Jiequn Han , Pilar Cossio , Luhuan Wu

The Gene or DNA sequence in every cell does not control genetic properties on its own; Rather, this is done through translation of DNA into protein and subsequent formation of a certain 3D structure. The biological function of a protein is…

Computational Engineering, Finance, and Science · Computer Science 2019-05-30 Leila Khalatbari , Mohammad Reza Kangavari , Saeid Hosseini , Hongzhi Yin , Ngai-Man Cheung

Counterfactual explanations for machine learning models are used to find minimal interventions to the feature values such that the model changes the prediction to a different output or a target output. A valid counterfactual explanation…

Machine Learning · Computer Science 2023-03-23 Shravan Kumar Sajja , Sumanta Mukherjee , Satyam Dwivedi
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