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Designing protein sequences with specific biological functions and structural stability is crucial in biology and chemistry. Generative models already demonstrated their capabilities for reliable protein design. However, previous models are…

Machine Learning · Computer Science 2024-02-28 Lin Zongying , Li Hao , Lv Liuzhenghao , Lin Bin , Zhang Junwu , Chen Calvin Yu-Chian , Yuan Li , Tian Yonghong

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

Designing novel functional proteins crucially depends on accurately modeling their fitness landscape. Given the limited availability of functional annotations from wet-lab experiments, previous methods have primarily relied on…

Machine Learning · Computer Science 2024-12-03 Zuobai Zhang , Pascal Notin , Yining Huang , Aurélie Lozano , Vijil Chenthamarakshan , Debora Marks , Payel Das , Jian Tang

Stochastic oscillations in individual cells are usually characterized by a non-monotonic power spectrum with an oscillatory autocorrelation function. Here we develop an analytical approach of stochastic oscillations in a minimal hybrid…

Molecular Networks · Quantitative Biology 2024-02-08 Chen Jia , Hong Qian , Michael Q. Zhang

An In Silico model to relate the properties of proteins to the structure, sequence, function and evolutionary history of proteins is shown. The derived ideal sequences for amino acid residues in proteins can then be considered as attractors…

Condensed Matter · Physics 2007-05-23 S. Bumble

In the protein sequence space, natural proteins form clusters of families which are characterized by their unique native folds whereas the great majority of random polypeptides are neither clustered nor foldable to unique structures. Since…

Biomolecules · Quantitative Biology 2018-02-06 Akira R. Kinjo

A fundamental challenge in protein design is the trade-off between generating structural diversity while preserving motif biological function. Current state-of-the-art methods, such as partial diffusion in RFdiffusion, often fail to resolve…

Quantitative Methods · Quantitative Biology 2025-10-22 Kevin Michalewicz , Chen Jin , Philip Alexander Teare , Tom Diethe , Mauricio Barahona , Barbara Bravi , Asher Mullokandov

This work introduces the generative fractional diffusion model for protein generation (ProT-GFDM), a novel generative framework that employs fractional stochastic dynamics for protein backbone structure modeling. This approach builds on the…

Quantitative Methods · Quantitative Biology 2025-05-01 Xiao Liang , Wentao Ma , Eric Paquet , Herna Lydia Viktor , Wojtek Michalowski

Generative models have achieved remarkable success in image, video, and text domains. Inspired by this, researchers have explored utilizing generative models to generate neural network parameters. However, these efforts have been limited by…

Artificial Intelligence · Computer Science 2024-08-05 Xiaolong Jin , Kai Wang , Dongwen Tang , Wangbo Zhao , Yukun Zhou , Junshu Tang , Yang You

We study a stochastic model of gene expression, in which protein production has a form of random bursts whose size distribution is arbitrary, whereas protein decay is a first-order reaction. We find exact analytical expressions for the time…

Biological Physics · Physics 2016-09-21 Jakub Jędrak , Anna Ochab-Marcinek

The computational design of novel protein structures has the potential to impact numerous scientific disciplines greatly. Toward this goal, we introduce FoldFlow, a series of novel generative models of increasing modeling power based on the…

The evolutionary trajectory of a protein through sequence space is constrained by function and three-dimensional (3D) structure. Residues in spatial proximity tend to co-evolve, yet attempts to invert the evolutionary record to identify…

Biomolecules · Quantitative Biology 2015-03-13 Debora S. Marks , Lucy J. Colwell , Robert Sheridan , Thomas A. Hopf , Andrea Pagnani , Riccardo Zecchina , Chris Sander

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

During their evolution, proteins explore sequence space via an interplay between random mutations and phenotypic selection. Here we build upon recent progress in reconstructing data-driven fitness landscapes for families of homologous…

Biomolecules · Quantitative Biology 2022-01-28 Matteo Bisardi , Juan Rodriguez-Rivas , Francesco Zamponi , Martin Weigt

Speciation is of fundamental importance to understanding the huge diversity of life on Earth. In contrast to current phenomenological models, we develop a biophysically motivated approach to study speciation involving the co-evolution of…

Populations and Evolution · Quantitative Biology 2015-05-18 Bhavin S. Khatri , Richard A. Goldstein

Autoregressive models can predict clinical events, but generating patient-conditioned multi-step trajectories that respond to intervention tokens and testing whether those responses preserve known pharmacological associations has received…

Machine Learning · Computer Science 2026-05-07 Chris Sainsbury , Feng Dong , Andreas Karwath

Designing protein-binding proteins with high affinity is critical in biomedical research and biotechnology. Despite recent advancements targeting specific proteins, the ability to create high-affinity binders for arbitrary protein targets…

Machine Learning · Computer Science 2025-11-03 Zhenqiao Song , Tiaoxiao Li , Lei Li , Martin Renqiang Min

Biological processes, functions, and properties are intricately linked to the ensemble of protein conformations, rather than being solely determined by a single stable conformation. In this study, we have developed P2DFlow, a generative…

Biological Physics · Physics 2025-03-05 Yaowei Jin , Qi Huang , Ziyang Song , Mingyue Zheng , Dan Teng , Qian Shi

Proteins, essential to biological systems, perform functions intricately linked to their three-dimensional structures. Understanding the relationship between protein structures and their amino acid sequences remains a core challenge in…

Quantitative Methods · Quantitative Biology 2024-11-04 Liang He , Peiran Jin , Yaosen Min , Shufang Xie , Lijun Wu , Tao Qin , Xiaozhuan Liang , Kaiyuan Gao , Yuliang Jiang , Tie-Yan Liu

The conformational landscape of proteins is crucial to understanding their functionality in complex biological processes. Traditional physics-based computational methods, such as molecular dynamics (MD) simulations, suffer from rare event…

Biomolecules · Quantitative Biology 2024-09-25 Yan Wang , Lihao Wang , Yuning Shen , Yiqun Wang , Huizhuo Yuan , Yue Wu , Quanquan Gu