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Proteins are miniature machines whose function depends on their three-dimensional (3D) structure. Determining this structure computationally remains an unsolved grand challenge. A major bottleneck involves selecting the most accurate…

Quantitative Methods · Quantitative Biology 2020-11-30 Stephan Eismann , Patricia Suriana , Bowen Jing , Raphael J. L. Townshend , Ron O. Dror

Recent advances in geometric deep learning and generative modeling have enabled the design of novel proteins with a wide range of desired properties. However, current state-of-the-art approaches are typically restricted to generating…

Biomolecules · Quantitative Biology 2025-08-26 Vsevolod Viliuga , Leif Seute , Nicolas Wolf , Simon Wagner , Arne Elofsson , Jan Stühmer , Frauke Gräter

We introduce ProteinWorkshop, a comprehensive benchmark suite for representation learning on protein structures with Geometric Graph Neural Networks. We consider large-scale pre-training and downstream tasks on both experimental and…

The local structure of a protein strongly impacts its function and interactions with other molecules. Therefore, a concise, informative representation of a local protein environment is essential for modeling and designing proteins and…

In this study, we tackle the challenging task of predicting secondary structures from protein primary sequences, a pivotal initial stride towards predicting tertiary structures, while yielding crucial insights into protein activity,…

Machine Learning · Computer Science 2025-11-18 Disha Varshney , Samarth Garg , Sarthak Tyagi , Deeksha Varshney , Nayan Deep , Asif Ekbal

The thesis is aimed to solve the template-free protein folding problem by tackling two important components: efficient sampling in vast conformation space, and design of knowledge-based potentials with high accuracy. We have proposed the…

Machine Learning · Computer Science 2013-11-13 Feng Zhao

Proteins populate a manifold in the high-dimensional sequence space whose geometrical structure guides their natural evolution. Leveraging recently-developed structure prediction tools based on transformer models, we first examine the…

Biomolecules · Quantitative Biology 2023-11-13 A. Zambon , R. Zecchina , G. Tiana

In recent years, deep learning techniques have made significant strides in molecular generation for specific targets, driving advancements in drug discovery. However, existing molecular generation methods present significant limitations:…

Machine Learning · Computer Science 2025-03-12 Taojie Kuang , Qianli Ma , Athanasios V. Vasilakos , Yu Wang , Qiang , Cheng , Zhixiang Ren

Proteins evolve through complex sequence spaces, with fitness landscapes serving as a conceptual framework that links sequence to function. Fitness landscapes can be smooth, where multiple similarly accessible evolutionary paths are…

Populations and Evolution · Quantitative Biology 2024-11-21 Mahakaran Sandhu , John Chen , Dana Matthews , Matthew A Spence , Sacha B Pulsford , Barnabas Gall , James Nichols , Nobuhiko Tokuriki , Colin J Jackson

This review article provides an overview of structurally oriented experimental datasets that can be used to benchmark protein force fields, focusing on data generated by nuclear magnetic resonance (NMR) spectroscopy and room temperature…

Deep neural networks such as AlphaFold and RoseTTAFold predict remarkably accurate structures of proteins compared to other algorithmic approaches. It is known that biologically small perturbations in the protein sequence do not lead to…

Biomolecules · Quantitative Biology 2021-09-21 Sumit Kumar Jha , Arvind Ramanathan , Rickard Ewetz , Alvaro Velasquez , Susmit Jha

Protein engineering is important for biomedical applications, but conventional approaches are often inefficient and resource-intensive. While deep learning (DL) models have shown promise, their training or implementation into protein…

Quantitative Methods · Quantitative Biology 2024-11-08 Yungeng Liu , Zan Chen , Yu Guang Wang , Yiqing Shen

Deep learning has transformed protein design, enabling accurate structure prediction, sequence optimization, and de novo protein generation. Advances in single-chain protein structure prediction via AlphaFold2, RoseTTAFold, ESMFold, and…

Machine Learning · Computer Science 2025-02-27 Gregory W. Kyro , Tianyin Qiu , Victor S. Batista

Classification of proteins based on their structure provides a valuable resource for studying protein structure, function and evolutionary relationships. With the rapidly increasing number of known protein structures, manual and…

Computational Engineering, Finance, and Science · Computer Science 2009-07-14 Oktie Hassanzadeh

Determining the different conformational states of a protein and the transition paths between them is key to fully understanding the relationship between biomolecular structure and function. This can be accomplished by sampling protein…

Biological Physics · Physics 2021-03-24 Venkata K. Ramaswamy , Chris G. Willcocks , Matteo T. Degiacomi

Proteins are the major building blocks of life, and actuators of almost all chemical and biophysical events in living organisms. Their native structures in turn enable their biological functions which have a fundamental role in drug design.…

Designing protein sequences that fold into a target 3-D structure, termed as the inverse folding problem, is central to protein engineering. However, it remains challenging due to the vast sequence space and the importance of local…

Quantitative Methods · Quantitative Biology 2026-03-17 Sazan Mahbub , Souvik Kundu , Eric P. Xing

The native structures of proteins, except for notable exceptions of intrinsically disordered proteins, in general take their most stable conformation in the physiological condition to maintain their structural framework so that their…

Biomolecules · Quantitative Biology 2021-10-26 Lyman Monroe , Daisuke Kihara

Experimental determination of protein function is resource-consuming. As an alternative, computational prediction of protein function has received attention. In this context, protein structural classification (PSC) can help, by allowing for…

Molecular Networks · Quantitative Biology 2020-03-17 Khalique Newaz , Mahboobeh Ghalehnovi , Arash Rahnama , Panos J. Antsaklis , Tijana Milenkovic

Despite recent advances in protein-ligand structure prediction, deep learning methods remain limited in their ability to accurately predict binding affinities, particularly for novel protein targets dissimilar from the training set. In…

Quantitative Methods · Quantitative Biology 2025-12-04 Michael Brocidiacono , James Wellnitz , Konstantin I. Popov , Alexander Tropsha