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Numerous cellular functions rely on protein$\unicode{x2013}$protein interactions. Efforts to comprehensively characterize them remain challenged however by the diversity of molecular recognition mechanisms employed within the proteome. Deep…

Biomolecules · Quantitative Biology 2023-12-08 Julia R. Rogers , Gergő Nikolényi , Mohammed AlQuraishi

Network neuroscience is the emerging discipline concerned with investigating the complex patterns of interconnections found in neural systems, and to identify principles with which to understand them. Within this discipline, one…

Neurons and Cognition · Quantitative Biology 2017-08-29 Richard F. Betzel , Danielle S. Bassett

Generative models emerge as promising candidates for novel sequence-data driven approaches to protein design, and for the extraction of structural and functional information about proteins deeply hidden in rapidly growing sequence…

Biomolecules · Quantitative Biology 2021-11-10 Jeanne Trinquier , Guido Uguzzoni , Andrea Pagnani , Francesco Zamponi , Martin Weigt

Deep Generative AI has been a long-standing essential topic in the machine learning community, which can impact a number of application areas like text generation and computer vision. The major paradigm to train a generative model is…

Machine Learning · Computer Science 2025-02-25 Yuanjiang Cao , Quan Z. Sheng , Julian McAuley , Lina Yao

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

Recently described stochastic models of protein evolution have demonstrated that the inclusion of structural information in addition to amino acid sequences leads to a more reliable estimation of evolutionary parameters. We present a…

Populations and Evolution · Quantitative Biology 2020-09-22 Michael Golden , Eduardo García-Portugués , Michael Sørensen , Kanti V. Mardia , Thomas Hamelryck , Jotun Hein

In recent years, the study of artificial intelligence (AI) has undergone a paradigm shift. This has been propelled by the groundbreaking capabilities of generative models both in supervised and unsupervised learning scenarios. Generative AI…

Machine Learning · Computer Science 2024-05-21 Sandeep Singh Sengar , Affan Bin Hasan , Sanjay Kumar , Fiona Carroll

Accurate protein structures are essential for understanding biological function, yet incorporating experimental data into protein generative models remains a major challenge. Most predictors of experimental observables are…

Machine Learning · Computer Science 2025-11-18 Nadav Bojan Sellam , Meital Bojan , Paul Schanda , Alex Bronstein

Generative Artificial Intelligence (AI) has rapidly advanced the field of computer vision by enabling machines to create and interpret visual data with unprecedented sophistication. This transformation builds upon a foundation of generative…

Computer Vision and Pattern Recognition · Computer Science 2025-04-22 Daochang Liu , Junyu Zhang , Anh-Dung Dinh , Eunbyung Park , Shichao Zhang , Ajmal Mian , Mubarak Shah , Chang Xu

The principled design and discovery of biologically- and physically-informed models of neuronal dynamics has been advancing since the mid-twentieth century. Recent developments in artificial intelligence (AI) have accelerated this progress.…

Neurons and Cognition · Quantitative Biology 2021-12-24 Mahta Ramezanian Panahi , Germán Abrevaya , Jean-Christophe Gagnon-Audet , Vikram Voleti , Irina Rish , Guillaume Dumas

Generative AI models have revolutionized various fields by enabling the creation of realistic and diverse data samples. Among these models, diffusion models have emerged as a powerful approach for generating high-quality images, text, and…

Computer Vision and Pattern Recognition · Computer Science 2024-02-27 Gaurav Raut , Apoorv Singh

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

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

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

Proteins are dynamic, adopting ensembles of conformations. The nature of this conformational heterogenity is imprinted in the raw electron density measurements obtained from X-ray crystallography experiments. Fitting an ensemble of protein…

Quantitative Methods · Quantitative Biology 2024-12-19 Sai Advaith Maddipatla , Nadav Bojan Sellam , Sanketh Vedula , Ailie Marx , Alex Bronstein

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

The de novo design of proteins refers to creating proteins with specific structures and functions that do not naturally exist. In recent years, the accumulation of high-quality protein structure and sequence data and technological…

Biomolecules · Quantitative Biology 2025-04-24 Yujie Qin , Ming He , Changyong Yu , Ming Ni , Xian Liu , Xiaochen Bo

Healthcare requires AI that is predictive, reliable, and data-efficient. However, recent generative models lack physical foundation and temporal reasoning required for clinical decision support. As scaling language models show diminishing…

Machine Learning · Computer Science 2025-11-21 Mohammad Areeb Qazi , Maryam Nadeem , Mohammad Yaqub

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

Tokenization is a promising path to multi-modal models capable of jointly understanding protein sequences, structure, and function. Existing protein structure tokenizers create tokens by pooling information from local neighborhoods, an…

Machine Learning · Computer Science 2026-02-09 Rohit Dilip , Ayush Varshney , David Van Valen