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Designing ligand-binding proteins, such as enzymes and biosensors, is essential in bioengineering and protein biology. One critical step in this process involves designing protein pockets, the protein interface binding with the ligand.…

Biomolecules · Quantitative Biology 2024-10-01 Zaixi Zhang , Marinka Zitnik , Qi Liu

Convolutional neural networks have been widely applied to medical image segmentation and have achieved considerable performance. However, the performance may be significantly affected by the domain gap between training data (source domain)…

Image and Video Processing · Electrical Eng. & Systems 2022-07-28 Junyan Lyu , Yiqi Zhang , Yijin Huang , Li Lin , Pujin Cheng , Xiaoying Tang

Across scientific domains, generating new models or optimizing existing ones while meeting specific criteria is crucial. Traditional machine learning frameworks for guided design use a generative model and a surrogate model (discriminator),…

Machine Learning · Computer Science 2024-05-29 Nataša Tagasovska , Vladimir Gligorijević , Kyunghyun Cho , Andreas Loukas

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

Proteins power a vast array of functional processes in living cells. The capability to create new proteins with designed structures and functions would thus enable the engineering of cellular behavior and development of protein-based…

Biomolecules · Quantitative Biology 2023-06-08 Yeqing Lin , Mohammed AlQuraishi

Designing proteins de novo with tailored structural, physicochemical, and functional properties remains a grand challenge in biotechnology, medicine, and materials science, due to the vastness of sequence space and the complex coupling…

Artificial Intelligence · Computer Science 2025-12-01 Fiona Y. Wang , Di Sheng Lee , David L. Kaplan , Markus J. Buehler

The linear sequence of amino acids determines protein structure and function. Protein design, known as the inverse of protein structure prediction, aims to obtain a novel protein sequence that will fold into the defined structure. Recent…

Biomolecules · Quantitative Biology 2023-02-22 Cheng Tan , Zhangyang Gao , Jun Xia , Bozhen Hu , Stan Z. Li

Sequence generative models are transforming protein engineering. However, no principled framework exists for conditioning these models on auxiliary information, such as experimental data, without additional training of a generative model.…

Machine Learning · Computer Science 2026-01-19 Junhao Xiong , Ishan Gaur , Maria Lukarska , Hunter Nisonoff , Luke M. Oltrogge , David F. Savage , Jennifer Listgarten

Protein classification tasks are essential in drug discovery. Real-world protein structures are dynamic, which will determine the properties of proteins. However, the existing machine learning methods, like ProNet (Wang et al., 2022a), only…

Quantitative Methods · Quantitative Biology 2024-03-27 Yi-Shan Lan , Pin-Yu Chen , Tsung-Yi Ho

Through evolution, nature has presented a set of remarkable protein materials, including elastins, silks, keratins and collagens with superior mechanical performances that play crucial roles in mechanobiology. However, going beyond natural…

Materials Science · Physics 2023-12-19 Bo Ni , David L. Kaplan , Markus J. Buehler

Accurate identification of protein binding sites is crucial for understanding biomolecular interaction mechanisms and for the rational design of drug targets. Traditional predictive methods often struggle to balance prediction accuracy with…

Machine Learning · Computer Science 2026-01-06 Weisen Yang , Hanqing Zhang , Wangren Qiu , Xuan Xiao , Weizhong Lin

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

We review the recent progress in computational approaches to protein design which builds on advances in statistical-mechanical protein folding theory. In particular, we evaluate the degeneracy of the protein code (i.e. how many sequences…

Condensed Matter · Physics 2007-05-23 E. I. Shakhnovich

Computational protein design (CPD) offers transformative potential for bioengineering, but current deep CPD models, focused on universal domains, struggle with function-specific designs. This work introduces a novel CPD paradigm tailored…

Quantitative Methods · Quantitative Biology 2024-11-28 Jiangbin Zheng , Ge Wang , Han Zhang , Stan Z. Li

Protein engineering is an emerging field in biotechnology that has the potential to revolutionize various areas, such as antibody design, drug discovery, food security, ecology, and more. However, the mutational space involved is too vast…

Biomolecules · Quantitative Biology 2023-07-28 Yuchi Qiu , Guo-Wei Wei

Generative modeling for protein engineering is key to solving fundamental problems in synthetic biology, medicine, and material science. We pose protein engineering as an unsupervised sequence generation problem in order to leverage the…

Motivation: Protein-to-genome alignment is critical to annotating genes in non-model organisms. While there are a few tools for this purpose, all of them were developed over ten years ago and did not incorporate the latest advances in…

Genomics · Quantitative Biology 2022-12-29 Heng Li

Recently, many generative models for de novo protein structure design have emerged. Yet, only few tackle the difficult task of directly generating fully atomistic structures jointly with the underlying amino acid sequence. This is…

Accurate prediction of protein function is essential for elucidating molecular mechanisms and advancing biological and therapeutic discovery. Yet experimental annotation lags far behind the rapid growth of protein sequence data.…

Biomolecules · Quantitative Biology 2026-03-27 Mehmet Efe Akça , Gökçe Uludoğan , Arzucan Özgür , İnci M. Baytaş

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…