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We review the recent progress in computational approaches to protein design which builds on advances in statistical-mechanical protein folding theory. In particular, we evaluate the degeneracy of the protein code (i.e. how many sequences…

Condensed Matter · Physics 2007-05-23 E. I. Shakhnovich

After AlphaFold won the Nobel Prize, protein prediction with deep learning once again became a hot topic. We comprehensively explore advanced deep learning methods applied to protein structure prediction and design. It begins by examining…

Generative machine learning models are increasingly being used to design novel proteins for therapeutic and biotechnological applications. However, the current methods mostly focus on the design of proteins with a fixed backbone structure,…

Biomolecules · Quantitative Biology 2025-03-04 Petr Kouba , Joan Planas-Iglesias , Jiri Damborsky , Jiri Sedlar , Stanislav Mazurenko , Josef Sivic

Generating novel and functional protein sequences is critical to a wide range of applications in biology. Recent advancements in conditional diffusion models have shown impressive empirical performance in protein generation tasks. However,…

Machine Learning · Computer Science 2025-12-04 Zinan Ling , Yi Shi , Brett McKinney , Da Yan , Yang Zhou , Bo Hui

Proteins play crucial roles in every cellular process by interacting with each other, with nucleic acids, metabolites, and other molecules. The resulting assemblies can be very large and intricate and pose challenges to experimental…

Biomolecules · Quantitative Biology 2021-03-16 Charlotte W. van Noort , Rodrigo V. Honorato , Alexandre M. J. J. Bonvin

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

Protein structures and functions are determined by a contiguous arrangement of amino acid sequences. Designing novel protein sequences and structures with desired geometry and functions is a complex task with large state spaces. Here we…

Chemical Physics · Physics 2022-09-01 Xeerak Agha , Nihang Fu , Jianjun Hu

Peptides play a pivotal role in a wide range of biological activities through participating in up to 40% protein-protein interactions in cellular processes. They also demonstrate remarkable specificity and efficacy, making them promising…

Biomolecules · Quantitative Biology 2024-02-09 Song Yin , Xuenan Mi , Diwakar Shukla

While many good textbooks are available on Protein Structure, Molecular Simulations, Thermodynamics and Bioinformatics methods in general, there is no good introductory level book for the field of Structural Bioinformatics. This book aims…

The protein folding problem has attracted an increasing attention from physicists. The problem has a flavor of statistical mechanics, but possesses the most common feature of most biological problems -- the profound effects of evolution. I…

Statistical Mechanics · Physics 2009-10-31 Chao Tang

The ability to computationally generate novel yet physically foldable protein structures could lead to new biological discoveries and new treatments targeting yet incurable diseases. Despite recent advances in protein structure prediction,…

Biomolecules · Quantitative Biology 2022-11-28 Kevin E. Wu , Kevin K. Yang , Rianne van den Berg , James Y. Zou , Alex X. Lu , Ava P. Amini

Computational protein design, i.e. inferring novel and diverse protein sequences consistent with a given structure, remains a major unsolved challenge. Recently, deep generative models that learn from sequences alone or from sequences and…

Biomolecules · Quantitative Biology 2021-11-15 Igor Melnyk , Payel Das , Vijil Chenthamarakshan , Aurelie Lozano

We study a fundamental problem in structure-based drug design -- generating molecules that bind to specific protein binding sites. While we have witnessed the great success of deep generative models in drug design, the existing methods are…

Biomolecules · Quantitative Biology 2022-11-15 Shitong Luo , Jiaqi Guan , Jianzhu Ma , Jian Peng

Proteins are dynamic molecular machines whose biological functions, spanning enzymatic catalysis, signal transduction, and structural adaptation, are intrinsically linked to their motions. Designing proteins with targeted dynamic…

Biomolecules · Quantitative Biology 2025-02-17 Bo Ni , Markus J. Buehler

Deep learning in \emph{de novo} protein design has achieved atomic-level fidelity. However, existing models remain largely non-deliberative: they directly synthesize molecular geometries without explicitly reasoning about which residues or…

Designing novel proteins with desired functions is crucial in biology and chemistry. However, most existing work focus on protein sequence design, leaving protein sequence and structure co-design underexplored. In this paper, we propose…

Machine Learning · Computer Science 2023-10-05 Zhenqiao Song , Yunlong Zhao , Yufei Song , Wenxian Shi , Yang Yang , Lei Li

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

Protein design with desirable properties has been a significant challenge for many decades. Generative artificial intelligence is a promising approach and has achieved great success in various protein generation tasks. Notably, diffusion…

Deep learning is an advanced technology that relies on large-scale data and complex models for feature extraction and pattern recognition. It has been widely applied across various fields, including computer vision, natural language…

Genomics · Quantitative Biology 2024-12-24 Yindan Luo , Jiaxin Cai

Protein structure prediction and folding are fundamental to understanding biology, with recent deep learning advances reshaping the field. Diffusion-based generative models have revolutionized protein design, enabling the creation of novel…

Machine Learning · Computer Science 2025-10-01 Yogesh Verma , Markus Heinonen , Vikas Garg