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Three-dimensional native states of natural proteins display recurring and hierarchical patterns. Yet, traditional graph-based modeling of protein structures is often limited to operate within a single fine-grained resolution, and lacks…

Machine Learning · Computer Science 2023-12-29 Allan dos Santos Costa , Ilan Mitnikov , Mario Geiger , Manvitha Ponnapati , Tess Smidt , Joseph Jacobson

Diffusion-based generative models represent the current state-of-the-art for image generation. However, standard diffusion models are based on Euclidean geometry and do not translate directly to manifold-valued data. In this work, we…

Machine Learning · Computer Science 2023-12-20 Yesukhei Jagvaral , Francois Lanusse , Rachel Mandelbaum

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

Proteins are sequences of amino acids that serve as the basic building blocks of living organisms. Despite rapidly growing databases documenting structural and functional information for various protein sequences, our understanding of…

Biomolecules · Quantitative Biology 2025-01-06 Weihang Dai

While DeepMind has tentatively solved protein folding, its inverse problem -- protein design which predicts protein sequences from their 3D structures -- still faces significant challenges. Particularly, the lack of large-scale standardized…

Quantitative Methods · Quantitative Biology 2022-02-15 Zhangyang Gao , Cheng Tan , Stan Z. Li

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

Self-supervised learning is a popular and powerful method for utilizing large amounts of unlabeled data, for which a wide variety of training objectives have been proposed in the literature. In this study, we perform a Bayesian analysis of…

Machine Learning · Computer Science 2023-02-08 Emanuele Sansone , Robin Manhaeve

Diffusion models offer a powerful means of capturing the manifold of realistic protein structures, enabling rapid design for protein engineering tasks. However, existing approaches observe critical failure modes when precise constraints are…

Biomolecules · Quantitative Biology 2026-03-27 Jacob K. Christopher , Austin Seamann , Jingyi Cui , Sagar Khare , Ferdinando Fioretto

Computational protein design facilitates discovery of novel proteins with prescribed structure and functionality. Exciting designs were recently reported using novel data-driven methodologies that can be roughly divided into two categories:…

Biological Physics · Physics 2023-03-28 Cyril Malbranke , David Bikard , Simona Cocco , Rémi Monasson , Jérôme Tubiana

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

The capability of accurate prediction of protein functions and properties is essential in the biotechnology industry, e.g. drug development and artificial protein synthesis, etc. The main challenges of protein function prediction are the…

Quantitative Methods · Quantitative Biology 2021-12-02 Wei-Cheng Tseng , Po-Han Chi , Jia-Hua Wu , Min Sun

This paper aims to address the challenge of data generation beyond the training data and proposes a framework for Structural Extrapolated Data GEneration (SEDGE) based on suitable assumptions on the underlying data-generating process. We…

Machine Learning · Computer Science 2026-05-15 Kun Zhang , Jiaqi Sun , Yiqing Li , Ignavier Ng , Namrata Deka , Shaoan Xie

Deep learning is catalyzing a scientific revolution fueled by big data, accessible toolkits, and powerful computational resources, impacting many fields including protein structural modeling. Protein structural modeling, such as predicting…

Biomolecules · Quantitative Biology 2020-07-17 Wenhao Gao , Sai Pooja Mahajan , Jeremias Sulam , Jeffrey J. Gray

Background: The inception of next generations sequencing technologies have exponentially increased the volume of biological sequence data. Protein sequences, being quoted as the `language of life', has been analyzed for a multitude of…

Quantitative Methods · Quantitative Biology 2020-12-08 Nabil Ibtehaz , S. M. Shakhawat Hossain Sourav , Md. Shamsuzzoha Bayzid , M. Sohel Rahman

Group equivariance (e.g. SE(3) equivariance) is a critical physical symmetry in science, from classical and quantum physics to computational biology. It enables robust and accurate prediction under arbitrary reference transformations. In…

Computational Engineering, Finance, and Science · Computer Science 2023-02-08 Weitao Du , He Zhang , Yuanqi Du , Qi Meng , Wei Chen , Bin Shao , Tie-Yan Liu

Self-supervised protein language models have proved their effectiveness in learning the proteins representations. With the increasing computational power, current protein language models pre-trained with millions of diverse sequences can…

Biomolecules · Quantitative Biology 2022-11-02 Ningyu Zhang , Zhen Bi , Xiaozhuan Liang , Siyuan Cheng , Haosen Hong , Shumin Deng , Jiazhang Lian , Qiang Zhang , Huajun Chen

Recent advancements in specialized large-scale architectures for training image and language have profoundly impacted the field of computer vision and natural language processing (NLP). Language models, such as the recent ChatGPT and GPT4…

Biomolecules · Quantitative Biology 2023-05-04 Sergio Romero-Romero , Sebastian Lindner , Noelia Ferruz

The advent of deep learning has introduced efficient approaches for de novo protein sequence design, significantly improving success rates and reducing development costs compared to computational or experimental methods. However, existing…

Artificial Intelligence · Computer Science 2024-07-11 Yutong Hu , Yang Tan , Andi Han , Lirong Zheng , Liang Hong , Bingxin Zhou

Function in natural systems arises from one-dimensional sequences forming three-dimensional structures with specific properties. However, current generative models suffer from critical limitations: training objectives seldom target function…

Protein structure generative models have seen a recent surge of interest, but meaningfully evaluating them computationally is an active area of research. While current metrics have driven useful progress, they do not capture how well models…

Biomolecules · Quantitative Biology 2025-07-25 Felix Faltings , Hannes Stark , Tommi Jaakkola , Regina Barzilay