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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

Protein folding and design are major biophysical problems, the solution of which would lead to important applications especially in medicine. Here a novel protein model capable of simultaneously provide quantitative protein design and…

Biological Physics · Physics 2015-06-22 Ivan Coluzza

Intrinsically disordered regions (IDRs) account for one-third of the human proteome and play essential biological roles. However, predicting the functions of IDRs remains a major challenge due to their lack of stable structures, rapid…

Biomolecules · Quantitative Biology 2025-07-04 Đesika Kolarić , Chi Fung Willis Chow , Rita Zi Zhu , Agnes Toth-Petroczy , T. Reid Alderson , Iva Pritišanac

Protein engineering is experiencing a paradigmatic shift through the integration of geometric deep learning into computational design workflows. While traditional strategies, such as rational design and directed evolution, have enabled…

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

Recent years have seen tremendous developments in the use of machine learning models to link amino acid sequence, structure and function of folded proteins. These methods are, however, rarely applicable to the wide range of proteins and…

Biomolecules · Quantitative Biology 2025-02-27 Sören von Bülow , Giulio Tesei , Kresten Lindorff-Larsen

Generative modeling has become a central paradigm in protein research, extending machine learning beyond structure prediction toward sequence design, backbone generation, inverse folding, and biomolecular interaction modeling. However, the…

Machine Learning · Computer Science 2026-03-30 Senura Hansaja Wanasekara , Minh-Duong Nguyen , Xiaochen Liu , Nguyen H. Tran , Ken-Tye Yong

The design of novel proteins has many applications but remains an attritional process with success in isolated cases. Meanwhile, deep learning technologies have exploded in popularity in recent years and are increasingly applicable to…

Biomolecules · Quantitative Biology 2018-11-07 Joe G Greener , Lewis Moffat , David T Jones

Computational protein design (CPD) offers transformative potential for bioengineering, but current deep CPD models, focused on universal domains, struggle with function-specific designs. This work introduces a novel CPD paradigm tailored…

Quantitative Methods · Quantitative Biology 2024-11-28 Jiangbin Zheng , Ge Wang , Han Zhang , Stan Z. Li

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

Intrinsically disordered proteins (IDPs) and multidomain proteins with flexible linkers show a high level of structural heterogeneity and are best described by ensembles consisting of multiple conformations with associated thermodynamic…

Biomolecules · Quantitative Biology 2021-12-13 F. Emil Thomasen , Kresten Lindorff-Larsen

Computational molecular design -- the endeavor to design molecules, with various missions, aided by machine learning and molecular dynamics approaches, has been widely applied to create valuable new molecular entities, from small molecule…

Protein engineering seeks to identify protein sequences with optimized properties. When guided by machine learning, protein sequence generation methods can draw on prior knowledge and experimental efforts to improve this process. In this…

Quantitative Methods · Quantitative Biology 2021-05-28 Zachary Wu , Kadina E. Johnston , Frances H. Arnold , Kevin K. Yang

The protein design problem involves finding polypeptide sequences folding into a given threedimensional structure. Its rigorous algorithmic solution is computationally demanding, involving a nested search in sequence and structure spaces.…

Quantum Physics · Physics 2024-07-11 Veronica Panizza , Philipp Hauke , Cristian Micheletti , Pietro Faccioli

Directed evolution of proteins has been the most effective method for protein engineering. However, a new paradigm is emerging, fusing the library generation and screening approaches of traditional directed evolution with computation…

Biomolecules · Quantitative Biology 2023-05-29 Kadina E. Johnston , Clara Fannjiang , Bruce J. Wittmann , Brian L. Hie , Kevin K. Yang , Zachary Wu

The 21st century is presenting humankind with unprecedented environmental and medical challenges. The ability to design novel proteins tailored for specific purposes could transform our ability to respond timely to these issues. Recent…

Biomolecules · Quantitative Biology 2022-08-24 Noelia Ferruz , Birte Höcker

The optimal design of compounds through manipulating properties at the molecular level is often the key to considerable scientific advances and improved process systems performance. This paper highlights key trends, challenges, and…

Biomolecules · Quantitative Biology 2020-07-13 Abdulelah S. Alshehri , Rafiqul Gani , Fengqi You

Deep learning approaches have produced substantial breakthroughs in fields such as image classification and natural language processing and are making rapid inroads in the area of protein design. Many generative models of proteins have been…

Machine Learning · Computer Science 2021-09-29 Alexey Strokach , Philip M. Kim

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

Protein design is a fundamental challenge in biotechnology, aiming to design novel sequences with specific functions within the vast space of possible proteins. Recent advances in deep generative models have enabled function-based protein…

Machine Learning · Computer Science 2025-10-15 Nuowei Liu , Jiahao Kuang , Yanting Liu , Tao Ji , Changzhi Sun , Man Lan , Yuanbin Wu