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Protein design has the potential to revolutionize biotechnology and medicine. While most efforts have focused on proteins with well-defined structures, increased recognition of the functional significance of intrinsically disordered…

Biomolecules · Quantitative Biology 2025-09-17 Giulio Tesei , Francesco Pesce , Kresten Lindorff-Larsen

Proteins are biomolecules of life. They fold into a great variety of three-dimensional (3D) shapes. Underlying these folding patterns are many recurrent structural fragments or building blocks (analogous to `LEGO bricks'). This paper…

Quantitative Methods · Quantitative Biology 2013-10-08 Arun S. Konagurthu , Arthur M. Lesk , David Abramson , Peter J. Stuckey , Lloyd Allison

As protein informatics advances rapidly, the demand for enhanced predictive accuracy, structural analysis, and functional understanding has intensified. Transformer models, as powerful deep learning architectures, have demonstrated…

Machine Learning · Computer Science 2025-05-28 Xiaowen Ling , Zhiqiang Li , Yanbin Wang , Zhuhong You

Generative modeling techniques such as Diffusion and Flow Matching have achieved significant successes in generating designable and diverse protein backbones. However, many current models are computationally expensive, requiring hundreds or…

Biomolecules · Quantitative Biology 2025-10-30 Junhua Chen , Simon Mathis , Charles Harris , Kieran Didi , Pietro Lio

An effective model for protein structures is important for the study of protein geometry, which, to a large extent, determine the functions of proteins. There are a number of approaches for modelling; one might focus on the conformation of…

Biomolecules · Quantitative Biology 2021-11-30 Jørgen Ellegaard Andersen , Jens Ledet Jensen , Yuki Koyanagi , Jakob Toudahl Nielsen , Rasmus Villemoes

Target proteins that lack accessible binding pockets and conformational stability have posed increasing challenges for drug development. Induced proximity strategies, such as PROTACs and molecular glues, have thus gained attention as…

Computational design of protein-binding proteins is a fundamental capability with broad utility in biomedical research and biotechnology. Recent methods have made strides against some target proteins, but on-demand creation of high-affinity…

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

The de novo design of ligand-binding proteins with tailored functions is essential for advancing biotechnology and molecular medicine, yet existing AI approaches are limited by scarce protein-ligand complex data. To circumvent this data…

Machine Learning · Computer Science 2026-03-03 Zhenqiao Song , Ramith Hettiarachchi , Chuan Li , Jianwen Xie , Lei Li

Consistency and reliability are crucial for conducting AI research. Many famous research fields, such as object detection, have been compared and validated with solid benchmark frameworks. After AlphaFold2, the protein folding task has…

Biomolecules · Quantitative Biology 2023-08-01 Jaemyung Lee , Kyeongtak Han , Jaehoon Kim , Hasun Yu , Youhan Lee

Engineering new molecules with desirable functions and properties has the potential to extend our ability to engineer proteins beyond what nature has so far evolved. Advances in the so-called "de novo" design problem have recently been…

Machine Learning · Computer Science 2023-10-17 Adam Winnifrith , Carlos Outeiral , Brian Hie

Motivation: Assigning statistical significance accurately has become increasingly important as meta data of many types, often assembled in hierarchies, are constructed and combined for further biological analyses. Statistical inaccuracy of…

Quantitative Methods · Quantitative Biology 2014-07-25 Gelio Alves , Yi-Kuo Yu

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

Deep generative models that learn from the distribution of natural protein sequences and structures may enable the design of new proteins with valuable functions. While the majority of today's models focus on generating either sequences or…

Biomolecules · Quantitative Biology 2024-10-03 Chentong Wang , Sarah Alamdari , Carles Domingo-Enrich , Ava Amini , Kevin K. Yang

Traditional drug discovery relies on rounds of screening millions of candidate molecules with low success rates, making drug discovery time and resource intensive. To overcome this screening bottleneck, we introduce Latent-X, an all-atom…

The accurate screening of candidate drug ligands against target proteins through computational approaches is of prime interest to drug development efforts. Such virtual screening depends in part on methods to predict the binding affinity…

Machine Learning · Computer Science 2024-10-22 Ho-Joon Lee , Prashant S. Emani , Mark B. Gerstein

Recently developed deep learning techniques have significantly improved the accuracy of various speech and image recognition systems. In this paper we adapt some of these techniques for protein secondary structure prediction. We first train…

Machine Learning · Computer Science 2016-11-07 Akosua Busia , Jasmine Collins , Navdeep Jaitly

Free energy calculations are rapidly becoming indispensable in structure-enabled drug discovery programs. As new methods, force fields, and implementations are developed, assessing their expected accuracy on real-world systems…

Protein generative models have shown remarkable promise in protein design, yet their success rates remain constrained by reliance on curated sequence-structure datasets and by misalignment between supervised objectives and real design…

Machine Learning · Computer Science 2026-03-03 Ziwen Wang , Jiajun Fan , Ruihan Guo , Thao Nguyen , Heng Ji , Ge Liu

Protein quality assessment (QA) has played an important role in protein structure prediction. We developed a novel single-model quality assessment method - Qprob. Qprob calculates the absolute error for each protein feature value against…

Quantitative Methods · Quantitative Biology 2016-07-15 Renzhi Cao , Jianlin Cheng