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Diffusion models produce impressive results in modalities ranging from images and video to protein design and text. However, generating samples with user-specified properties remains a challenge. Recent research proposes fine-tuning models…

Machine Learning · Computer Science 2025-07-21 Raghav Singhal , Zachary Horvitz , Ryan Teehan , Mengye Ren , Zhou Yu , Kathleen McKeown , Rajesh Ranganath

Conditional Flow Matching(CFM) represents a fast and high-quality approach to generative modelling, but in many applications it is of interest to steer the generated samples towards precise requirements. While steering approaches like…

Machine Learning · Computer Science 2025-09-03 Konstantin Mark , Leonard Galustian , Maximilian P. -P. Kovar , Esther Heid

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…

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

Discrete diffusion models have recently emerged as a promising alternative to the autoregressive approach for generating discrete sequences. Sample generation via gradual denoising or demasking processes allows them to capture hierarchical…

Diffusion models offer a powerful means of capturing the manifold of realistic protein structures, enabling rapid design for protein engineering tasks. However, existing approaches observe critical failure modes when precise constraints are…

Biomolecules · Quantitative Biology 2026-03-27 Jacob K. Christopher , Austin Seamann , Jingyi Cui , Sagar Khare , Ferdinando Fioretto

AI-assisted protein design has emerged as a critical tool for advancing biotechnology, as deep generative models have demonstrated their reliability in this domain. However, most existing models primarily utilize protein sequence or…

Computational Engineering, Finance, and Science · Computer Science 2026-05-27 Changjian Zhou , Yuexi Qiu , Jia Song

Protein fitness optimization involves finding a protein sequence that maximizes desired quantitative properties in a combinatorially large design space of possible sequences. Recent advances in steering protein generative models (e.g.,…

Biomolecules · Quantitative Biology 2025-10-22 Jason Yang , Wenda Chu , Daniel Khalil , Raul Astudillo , Bruce J. Wittmann , Frances H. Arnold , Yisong Yue

Generative modeling of discrete data underlies important applications spanning text-based agents like ChatGPT to the design of the very building blocks of life in protein sequences. However, application domains need to exert control over…

Reaction-diffusion (Turing) systems are fundamental to the formation of spatial patterns in nature and engineering. These systems are governed by a set of non-linear partial differential equations containing parameters that determine the…

Machine Learning · Computer Science 2022-11-28 Jordon Kho , Winston Koh , Jian Cheng Wong , Pao-Hsiung Chiu , Chin Chun Ooi

Generative artificial intelligence models learn probability distributions from data and produce novel samples that capture the salient properties of their training sets. Proteins are particularly attractive for such approaches given their…

Biomolecules · Quantitative Biology 2026-02-27 Filippo Stocco , Michele Garibbo , Noelia Ferruz

Guiding unconditional diffusion models typically requires either retraining with conditional inputs or per-step gradient computations (e.g., classifier-based guidance), both of which incur substantial computational overhead. We present a…

Machine Learning · Computer Science 2026-02-13 Qingsong Wang , Mikhail Belkin , Yusu Wang

Protein family design emerges as a promising alternative by combining the advantages of de novo protein design and mutation-based directed evolution.In this paper, we propose ProfileBFN, the Profile Bayesian Flow Networks, for specifically…

Biomolecules · Quantitative Biology 2025-02-25 Jingjing Gong , Yu Pei , Siyu Long , Yuxuan Song , Zhe Zhang , Wenhao Huang , Ziyao Cao , Shuyi Zhang , Hao Zhou , Wei-Ying Ma

Recent advances in protein backbone generation have achieved promising results under structural, functional, or physical constraints. However, existing methods lack the flexibility for precise topology control, limiting navigation of the…

Artificial Intelligence · Computer Science 2025-04-22 Zhengxi Lu , Shizhuo Cheng , Yuru Jiang , Yan Zhang , Min Zhang

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

While score-based generative models are the model of choice across diverse domains, there are limited tools available for controlling inference-time behavior in a principled manner, e.g. for composing multiple pretrained models. Existing…

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

Inverse design problems are common in engineering and materials science. The forward direction, i.e., computing output quantities from design parameters, typically requires running a numerical simulation, such as a FEM, as an intermediate…

Machine Learning · Computer Science 2026-02-18 Jens U. Kreber , Christian Weißenfels , Joerg Stueckler

Guided or controlled data generation with diffusion models\blfootnote{Partial preliminary results of this work appeared in International Conference on Machine Learning 2025 \citep{li2025provable}.} has become a cornerstone of modern…

Machine Learning · Statistics 2025-12-05 Yuchen Jiao , Yuxin Chen , Gen Li

This study presents a generative optimization framework that builds on a fine-tuned diffusion model and reward-directed sampling to generate high-performance engineering designs. The framework adopts a parametric representation of the…

Machine Learning · Computer Science 2025-08-05 Hadi Keramati , Patrick Kirchen , Mohammed Hannan , Rajeev K. Jaiman
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