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The design of protein sequences with desired functionalities is a fundamental task in protein engineering. Deep generative methods, such as autoregressive models and diffusion models, have greatly accelerated the discovery of novel protein…

Machine Learning · Computer Science 2025-04-16 Zitai Kong , Yiheng Zhu , Yinlong Xu , Hanjing Zhou , Mingzhe Yin , Jialu Wu , Hongxia Xu , Chang-Yu Hsieh , Tingjun Hou , Jian Wu

Effective representations of protein sequences are widely recognized as a cornerstone of machine learning-based protein design. Yet, protein bioengineering poses unique challenges for sequence representation, as experimental datasets…

Quantitative Methods · Quantitative Biology 2026-04-07 Ana F. Rodrigues , Lucas Ferraz , Laura Balbi , Pedro Giesteira Cotovio , Catia Pesquita

Much scientific enquiry across disciplines is founded upon a mechanistic treatment of dynamic systems that ties form to function. A highly visible instance of this is in molecular biology, where an important goal is to determine…

Biomolecules · Quantitative Biology 2021-06-17 Xiaojie Guo , Yuanqi Du , Sivani Tadepalli , Liang Zhao , Amarda Shehu

Protein language models (pLMs) have demonstrated success at generating functional proteins across vast sequence spaces but lack the ability to design high-fitness variants on demand. Here, we iteratively guide pLMs toward user-defined…

Biomolecules · Quantitative Biology 2025-12-01 Filippo Stocco , Maria Artigues-Lleixa , Andrea Hunklinger , Talal Widatalla , Marc Guell , Noelia Ferruz

Protein design with desirable properties has been a significant challenge for many decades. Generative artificial intelligence is a promising approach and has achieved great success in various protein generation tasks. Notably, diffusion…

We report a flexible language-model based deep learning strategy, applied here to solve complex forward and inverse problems in protein modeling, based on an attention neural network that integrates transformer and graph convolutional…

Biomolecules · Quantitative Biology 2023-10-20 Markus J. Buehler

In recent years machine learning (ML) took bio- and cheminformatics fields by storm, providing new solutions for a vast repertoire of problems related to protein sequence, structure, and interactions analysis. ML techniques, deep neural…

Biomolecules · Quantitative Biology 2020-03-31 Marta M. Stepniewska-Dziubinska , Piotr Zielenkiewicz , Pawel Siedlecki

We introduce Concept Bottleneck Protein Language Models (CB-pLM), a generative masked language model with a layer where each neuron corresponds to an interpretable concept. Our architecture offers three key benefits: i) Control: We can…

Molecular dynamics (MD) simulation has long been the principal computational tool for exploring protein conformational landscapes and dynamics, but its application is limited by high computational cost. We present ProTDyn, a foundation…

Biological Physics · Physics 2025-10-02 Yikai Liu , Haoyang Zheng , Lining Mao , Yanbin Wang , Ming Chen , Guang Lin

The goal of protein representation learning is to extract knowledge from protein databases that can be applied to various protein-related downstream tasks. Although protein sequence, structure, and function are the three key modalities for…

Biomolecules · Quantitative Biology 2024-05-14 Eunji Ko , Seul Lee , Minseon Kim , Dongki Kim

In recent years, natural language processing (NLP) models have demonstrated remarkable capabilities in various domains beyond traditional text generation. In this work, we introduce PeptideGPT, a protein language model tailored to generate…

Machine Learning · Computer Science 2024-10-28 Aayush Shah , Chakradhar Guntuboina , Amir Barati Farimani

Generative models have recently advanced $\textit{de novo}$ protein design by learning the statistical regularities of natural structures. However, current approaches face three key limitations: (1) Existing methods cannot jointly learn…

Machine Learning · Computer Science 2026-03-09 Zhanghan Ni , Yanjing Li , Zeju Qiu , Bernhard Schölkopf , Hongyu Guo , Weiyang Liu , Shengchao Liu

In this and the associated article 'BioBlender: A Software for Intuitive Representation of Surface Properties of Biomolecules', (Andrei et al) we present BioBlender as a complete instrument for the elaboration of motion (here) and the…

Biomolecules · Quantitative Biology 2010-09-27 Maria Francesca Zini , Yuri Porozov , Raluca Mihaela Andrei , Tiziana Loni , Claudia Caudai , Monica Zoppè

Current protein language models (pLMs) predominantly focus on single-chain protein sequences and often have not accounted for constraints on generative design imposed by protein-protein interactions. To address this gap, we present paired…

Biomolecules · Quantitative Biology 2023-11-22 Simon K. S. Chu , Kathy Y. Wei

By exact computer enumeration and combinatorial methods, we have calculated the designability of proteins in a simple lattice H-P model for the protein folding problem. We show that if the strength of the non-additive part of the…

Soft Condensed Matter · Physics 2009-10-30 M. R. Ejtehadi , N. Hamedani , H. Seyed-Allaei , V. Shahrezaei , M. Yahyanejad

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

Spider silks are remarkable materials characterized by superb mechanical properties such as strength, extensibility and lightweightedness. Yet, to date, limited models are available to fully explore sequence-property relationships for…

Materials Science · Physics 2023-10-20 Wei Lu , David L. Kaplan , Markus J. Buehler

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

Multimodal models that jointly reason over protein sequences, structures, and function annotations within a unified representation hold immense potential for integrating multimodal data and generating new proteins with designed functional…

Biomolecules · Quantitative Biology 2026-05-12 Nabin Giri , Steven Farrell , Kristofer E. Bouchard

Learning meaningful protein representation is important for a variety of biological downstream tasks such as structure-based drug design. Having witnessed the success of protein sequence pretraining, pretraining for structural data which is…

Machine Learning · Computer Science 2023-02-23 Yufei Huang , Lirong Wu , Haitao Lin , Jiangbin Zheng , Ge Wang , Stan Z. Li
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