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Protein design often begins with the knowledge of a desired function from a motif which motif-scaffolding aims to construct a functional protein around. Recently, generative models have achieved breakthrough success in designing scaffolds…

Construction of a scaffold structure that supports a desired motif, conferring protein function, shows promise for the design of vaccines and enzymes. But a general solution to this motif-scaffolding problem remains open. Current…

Biomolecules · Quantitative Biology 2023-03-21 Brian L. Trippe , Jason Yim , Doug Tischer , David Baker , Tamara Broderick , Regina Barzilay , Tommi Jaakkola

The interaction between proteins and DNA is a key driving force in a significant number of biological processes such as transcriptional regulation, repair, recombination, splicing, and DNA modification. The identification of DNA-binding…

Quantitative Methods · Quantitative Biology 2017-05-10 Hamid Reza Hassanzadeh , Pushkar Kolhe , Charles L. Isbell , May D. Wang

Function-guided protein design is a crucial task with significant applications in drug discovery and enzyme engineering. However, the field lacks a unified and comprehensive evaluation framework. Current models are assessed using…

Machine Learning · Computer Science 2025-09-30 Jiahao Kuang , Nuowei Liu , Jie Wang , Changzhi Sun , Tao Ji , Yuanbin Wu

Motif scaffolding seeks to design scaffold structures for constructing proteins with functions derived from the desired motif, which is crucial for the design of vaccines and enzymes. Previous works approach the problem by inpainting or…

Biomolecules · Quantitative Biology 2024-06-06 Ke Liu , Weian Mao , Shuaike Shen , Xiaoran Jiao , Zheng Sun , Hao Chen , Chunhua Shen

Proteins perform critical processes in all living systems: converting solar energy into chemical energy, replicating DNA, as the basis of highly performant materials, sensing and much more. While an incredible range of functionality has…

Biomolecules · Quantitative Biology 2021-09-29 Leonardo V. Castorina , Rokas Petrenas , Kartic Subr , Christopher W. Wood

Motif extraction is an important task in motif based molecular representation learning. Previously, machine learning approaches employing either rule-based or string-based techniques to extract motifs. Rule-based approaches may extract…

Quantitative Methods · Quantitative Biology 2023-12-27 Zhaoning Yu , Hongyang Gao

Many protein design applications, such as binder or enzyme design, require scaffolding a structural motif with high precision. Generative modelling paradigms based on denoising diffusion processes emerged as a leading candidate to address…

Machine Learning · Computer Science 2024-03-15 Kieran Didi , Francisco Vargas , Simon V Mathis , Vincent Dutordoir , Emile Mathieu , Urszula J Komorowska , Pietro Lio

Recent advances in de novo protein binder design have enabled increasing experimental validation, yet reported in silico metrics remain difficult to interpret or compare across studies due to non-standardized evaluation protocols. We…

Quantitative Methods · Quantitative Biology 2026-05-25 Cong Liu , Milong Ren , Jiaqi Guan , Chengyue Gong , Jinyuan Sun , Xinshi Chen , Wenzhi Xiao

Proteins are the fundamental macromolecules that play diverse and crucial roles in all living matter and have tremendous implications in healthcare, manufacturing, and biotechnology. Their functions are largely determined by the sequences…

Biomolecules · Quantitative Biology 2024-09-17 Boqiao Lai

This study investigates the current landscape and future directions of protein foundation model research. While recent advancements have transformed protein science and engineering, the field lacks a comprehensive benchmark for fair…

Biomolecules · Quantitative Biology 2025-06-19 Zhangyang Gao , Hao Wang , Cheng Tan , Chenrui Xu , Mengdi Liu , Bozhen Hu , Linlin Chao , Xiaoming Zhang , Stan Z. Li

This article introduces idMotif, a visual analytics framework designed to aid domain experts in the identification of motifs within protein sequences. Motifs, short sequences of amino acids, are critical for understanding the distinct…

Quantitative Methods · Quantitative Biology 2024-02-12 Ji Hwan Park , Vikash Prasad , Sydney Newsom , Fares Najar , Rakhi Rajan

SE(3)-based generative models have shown great promise in protein geometry modeling and effective structure design. However, the field currently lacks a modularized benchmark to enable comprehensive investigation and fair comparison of…

Machine Learning · Computer Science 2025-07-29 Lang Yu , Zhangyang Gao , Cheng Tan , Qin Chen , Jie Zhou , Liang He

A fundamental challenge in protein design is the trade-off between generating structural diversity while preserving motif biological function. Current state-of-the-art methods, such as partial diffusion in RFdiffusion, often fail to resolve…

Quantitative Methods · Quantitative Biology 2025-10-22 Kevin Michalewicz , Chen Jin , Philip Alexander Teare , Tom Diethe , Mauricio Barahona , Barbara Bravi , Asher Mullokandov

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

Protein design aims to compose amino-acid sequences that fold into stable three-dimensional structures while satisfying targeted functional properties. The field is increasingly shifting toward vibe protein design, where a single model is…

A common problem in bioinformatics is related to identifying gene regulatory regions marked by relatively high frequencies of motifs, or deoxyribonucleic acid sequences that often code for transcription and enhancer proteins. Predicting…

Genomics · Quantitative Biology 2021-01-22 Ethan Jacob Moyer , Anup Das

Frequent and structurally related subgraphs, also known as network motifs, are valuable features of many graph datasets. However, the high computational complexity of identifying motif sets in arbitrary datasets (motif mining) has limited…

Machine Learning · Computer Science 2022-06-08 Carlos Oliver , Dexiong Chen , Vincent Mallet , Pericles Philippopoulos , Karsten Borgwardt

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

Protein diffusion models have emerged as a promising approach for protein design. One such pioneering model is Genie, a method that asymmetrically represents protein structures during the forward and backward processes, using simple…

Biomolecules · Quantitative Biology 2024-05-27 Yeqing Lin , Minji Lee , Zhao Zhang , Mohammed AlQuraishi
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