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We introduce a generative model for protein backbone design utilizing geometric products and higher order message passing. In particular, we propose Clifford Frame Attention (CFA), an extension of the invariant point attention (IPA)…

Machine Learning · Computer Science 2024-11-11 Simon Wagner , Leif Seute , Vsevolod Viliuga , Nicolas Wolf , Frauke Gräter , Jan Stühmer

Several algorithms for RNA inverse folding have been used to design synthetic riboswitches, ribozymes and thermoswitches, whose activity has been experimentally validated. The RNAiFold software is unique among approaches for inverse folding…

Biomolecules · Quantitative Biology 2015-05-29 Juan Antonio Garcia-Martin , Ivan Dotu , Peter Clote

How proteins fold remains a central unsolved problem in biology. While the idea of a folding code embedded in the amino acid sequence was introduced more than 6 decades ago, this code remains undefined. While we now have powerful predictive…

Biomolecules · Quantitative Biology 2025-11-04 Carlos Bustamante , Christian Kaiser , Erik Lindahl , Robert Sosa , Giovanni Volpe

The design of \emph{de novo} functional proteins that bind specific ligand molecules is paramount in therapeutics and bio-engineering. A critical yet formidable task in this endeavor is the design of the protein pocket, which is the cavity…

Biomolecules · Quantitative Biology 2023-10-23 Zaixi Zhang , Zepu Lu , Zhongkai Hao , Marinka Zitnik , Qi Liu

Efficient design and discovery of target-driven molecules is a critical step in facilitating lead optimization in drug discovery. Current approaches to develop molecules for a target protein are intuition-driven, hampered by slow iterative…

Machine Learning · Computer Science 2022-05-24 Andrew D. McNaughton , Mridula S. Bontha , Carter R. Knutson , Jenna A. Pope , Neeraj Kumar

We propose a new way of looking at global optimization of off-lattice protein models. We present a dual optimization concept of predicting optimal sequences as well as optimal folds. We validate the utility of the recently introduced…

Computational Physics · Physics 2012-05-22 István Kolossváry , Kevin J. Bowers

We propose and discuss a novel strategy for protein design. The method is based on recent theoretical advancements which showed the importance to treat carefully the conformational free energy of designed sequences. In this work we show how…

Statistical Mechanics · Physics 2009-10-31 A. Rossi , A. Maritan , C. Micheletti

This paper presents a method of reconstruction a primary structure of a protein that folds into a given geometrical shape. This method predicts the primary structure of a protein and restores its linear sequence of amino acids in the…

Quantitative Methods · Quantitative Biology 2017-01-04 Andrii Riazanov , Mikhail Karasikov , Sergei Grudinin

Protein binder design is central to therapeutics, diagnostics, and synthetic biology, yet practical deployment remains challenging due to fragmented workflows, high computational costs, and complex tool integration. We present…

Biomolecules · Quantitative Biology 2025-05-29 Jie Gao , Jun Li , Jing Hu , Shanzhuo Zhang , Kunrui Zhu , Yueyang Huang , Xiaonan Zhang , Xiaomin Fang

Recent advances in structure-based protein design have accelerated de novo binder generation, yet interfaces on large domains or spanning multiple domains remain challenging due to high computational cost and declining success with…

Biomolecules · Quantitative Biology 2025-10-03 Zhenfeng Deng , Ruijie Hou , Ningrui Xie , Mike Tyers , Michał Koziarski

The fold recognition methods are promissing tools for capturing the structure of a protein by its amino acid residues sequence but their use is still restricted by the needs of huge computational resources and suitable efficient algorithms…

Quantitative Methods · Quantitative Biology 2007-07-30 Rumen Andonov , Guillaume Collet , Jean-François Gibrat , Antoine Marin , Vincent Poirriez , Nikola Yanev

The accuracy of AlphaFold2, a frontier end-to-end structure prediction system, is already close to that of the experimental determination techniques. Due to the complex model architecture and large memory consumption, it requires lots of…

Distributed, Parallel, and Cluster Computing · Computer Science 2022-11-02 Guoxia Wang , Zhihua Wu , Xiaomin Fang , Yingfei Xiang , Yiqun Liu , Dianhai Yu , Yanjun Ma

The growing significance of RNA engineering in diverse biological applications has spurred interest in developing AI methods for structure-based RNA design. While diffusion models have excelled in protein design, adapting them for RNA…

Biomolecules · Quantitative Biology 2024-06-11 Divya Nori , Wengong Jin

Computational protein design has a wide variety of applications. Despite its remarkable success, designing a protein for a given structure and function is still a challenging task. On the other hand, the number of solved protein structures…

Quantitative Methods · Quantitative Biology 2018-04-26 Jingxue Wang , Huali Cao , John Z. H. Zhang , Yifei Qi

We present FrameFlow, a method for fast protein backbone generation using SE(3) flow matching. Specifically, we adapt FrameDiff, a state-of-the-art diffusion model, to the flow-matching generative modeling paradigm. We show how flow…

Data-driven predictive methods which can efficiently and accurately transform protein sequences into biologically active structures are highly valuable for scientific research and medical development. Determining accurate folding landscape…

Structure determination is key to understanding protein function at a molecular level. Whilst significant advances have been made in predicting structure and function from amino acid sequence, researchers must still rely on expensive,…

Computer Vision and Pattern Recognition · Computer Science 2020-09-01 Alexander Hudson , Shaogang Gong

Addressing the growing demands of artificial intelligence (AI) and data analytics requires new computing approaches. In this paper, we propose a reconfigurable hardware accelerator designed specifically for AI and data-intensive…

Hardware Architecture · Computer Science 2026-02-05 Md Rownak Hossain Chowdhury , Mostafizur Rahman

Lightweight inference is critical for biomolecular structure prediction and downstream tasks, enabling efficient real-world deployment and inference-time scaling for large-scale applications. While AF3 and its variants (e.g., Protenix,…

Quantitative Methods · Quantitative Biology 2025-10-17 Bo Qiang , Chengyue Gong , Xinshi Chen , Yuxuan Zhang , Wenzhi Xiao

AlphaFold 3 represents a transformative advancement in computational biology, enhancing protein structure prediction through novel multi-scale transformer architectures, biologically informed cross-attention mechanisms, and geometry-aware…

Biomolecules · Quantitative Biology 2025-08-27 Alireza Abbaszadeh , Armita Shahlaee