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Recently, diffusion- and flow-based generative models of protein structures have emerged as a powerful tool for de novo protein design. Here, we develop Proteina, a new large-scale flow-based protein backbone generator that utilizes…

Adeno-associated viral (AAV) vectors are widely used delivery platforms in gene therapy, and the design of improved capsids is key to expanding their therapeutic potential. A central challenge in AAV bioengineering, as in protein design…

Directed evolution is a versatile technique in protein engineering that mimics the process of natural selection by iteratively alternating between mutagenesis and screening in order to search for sequences that optimize a given property of…

Biomolecules · Quantitative Biology 2024-05-02 Lixue Cheng , Ziyi Yang , Changyu Hsieh , Benben Liao , Shengyu Zhang

Designing proteins with desired functions or properties represents a core goal in synthetic biology and drug discovery. Recent advances in protein language models (PLMs) have enabled the generation of highly designable protein sequences,…

Machine Learning · Computer Science 2026-05-12 Yulin Zhang , He Cao , Zihao Jiang , Chenyi Zi , Zhipeng Zhou , Zijing Liu , Yu Li , Jia Li , Ziqi Gao

Generative models emerge as promising candidates for novel sequence-data driven approaches to protein design, and for the extraction of structural and functional information about proteins deeply hidden in rapidly growing sequence…

Biomolecules · Quantitative Biology 2021-11-10 Jeanne Trinquier , Guido Uguzzoni , Andrea Pagnani , Francesco Zamponi , Martin Weigt

Protein language models (PLMs) encode rich biological information, yet their internal neuron representations are poorly understood. We introduce the first automated framework for labeling every neuron in a PLM with biologically grounded…

Machine Learning · Computer Science 2025-07-10 Arjun Banerjee , David Martinez , Camille Dang , Ethan Tam

The conformational landscape of proteins is crucial to understanding their functionality in complex biological processes. Traditional physics-based computational methods, such as molecular dynamics (MD) simulations, suffer from rare event…

Biomolecules · Quantitative Biology 2024-09-25 Yan Wang , Lihao Wang , Yuning Shen , Yiqun Wang , Huizhuo Yuan , Yue Wu , Quanquan Gu

Designing protein sequences with specific biological functions and structural stability is crucial in biology and chemistry. Generative models already demonstrated their capabilities for reliable protein design. However, previous models are…

Machine Learning · Computer Science 2024-02-28 Lin Zongying , Li Hao , Lv Liuzhenghao , Lin Bin , Zhang Junwu , Chen Calvin Yu-Chian , Yuan Li , Tian Yonghong

Proteins play essential roles in nature, from catalyzing biochemical reactions to binding specific targets. Advances in protein engineering have the potential to revolutionize biotechnology and healthcare by designing proteins with tailored…

Biomolecules · Quantitative Biology 2025-05-05 Hocheol Lim , Geon-Ho Lee , Kyoung Tai No

Generative modeling of discrete data underlies important applications spanning text-based agents like ChatGPT to the design of the very building blocks of life in protein sequences. However, application domains need to exert control over…

We propose and analyse a variant of the recently introduced kinetic based optimization method that incorporates ideas like survival-of-the-fittest and mutation strategies well-known from genetic algorithms. Thus, we provide a first attempt…

Optimization and Control · Mathematics 2024-07-18 Giacomo Albi , Federica Ferrarese , Claudia Totzeck

The ability to engineer novel proteins with higher fitness for a desired property would be revolutionary for biotechnology and medicine. Modeling the combinatorially large space of sequences is infeasible; prior methods often constrain…

Biomolecules · Quantitative Biology 2024-03-05 Andrew Kirjner , Jason Yim , Raman Samusevich , Shahar Bracha , Tommi Jaakkola , Regina Barzilay , Ila Fiete

Advances in deep learning have opened an era of abundant and accurate predicted protein structures; however, similar progress in protein ensembles has remained elusive. This review highlights several recent research directions towards…

Biomolecules · Quantitative Biology 2025-09-23 Bowen Jing , Bonnie Berger , Tommi Jaakkola

Deep learning has been widely used for protein engineering. However, it is limited by the lack of sufficient experimental data to train an accurate model for predicting the functional fitness of high-order mutants. Here, we develop SESNet,…

Quantitative Methods · Quantitative Biology 2023-04-10 Mingchen Li , Liqi Kang , Yi Xiong , Yu Guang Wang , Guisheng Fan , Pan Tan , Liang Hong

Antibody therapeutics are among the most successful modern medicines, yet computationally designing antibodies with desirable binding and developability properties remains challenging. While protein language models (pLMs) have emerged as…

Machine Learning · Computer Science 2026-05-11 Justin Sanders , Luca Giancardo , Lan Guo , Yue Zhao , Kemal Sonmez , Nina Cheng , Melih Yilmaz

Protein is linked to almost every life process. Therefore, analyzing the biological structure and property of protein sequences is critical to the exploration of life, as well as disease detection and drug discovery. Traditional protein…

Machine Learning · Computer Science 2021-12-08 Yijia Xiao , Jiezhong Qiu , Ziang Li , Chang-Yu Hsieh , Jie Tang

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

In post genomic era with the advent of new technologies a huge amount of complex molecular data are generated with high throughput. The management of this biological data is definitely a challenging task due to complexity and heterogeneity…

Databases · Computer Science 2014-03-13 Ananya Bose , Suprativ Saha

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

Researchers have been studying approaches to steer the behavior of Large Language Models (LLMs) and build personalized LLMs tailored for various applications. While fine-tuning seems to be a direct solution, it requires substantial…

Computation and Language · Computer Science 2024-07-31 Yuanpu Cao , Tianrong Zhang , Bochuan Cao , Ziyi Yin , Lu Lin , Fenglong Ma , Jinghui Chen