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This tutorial provides an in-depth guide on inference-time guidance and alignment methods for optimizing downstream reward functions in diffusion models. While diffusion models are renowned for their generative modeling capabilities,…

Artificial Intelligence · Computer Science 2025-01-22 Masatoshi Uehara , Yulai Zhao , Chenyu Wang , Xiner Li , Aviv Regev , Sergey Levine , Tommaso Biancalani

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

Motivation: In recent years, protein function prediction has broken through the bottleneck of sequence features, significantly improving prediction accuracy using high-precision protein structures predicted by AlphaFold2. While…

Machine Learning · Computer Science 2025-04-01 Beibei Wang , Boyue Cui , Shiqu Chen , Xuan Wang , Yadong Wang , Junyi Li

Therapeutic peptides represent a unique class of pharmaceutical agents crucial for the treatment of human diseases. Recently, deep generative models have exhibited remarkable potential for generating therapeutic peptides, but they only…

Quantitative Methods · Quantitative Biology 2024-01-05 Yongkang Wang , Xuan Liu , Feng Huang , Zhankun Xiong , Wen Zhang

High-dimensional design spaces underpin a wide range of physics-based modeling and computational design tasks in science and engineering. These problems are commonly formulated as constrained black-box searches over rugged objective…

Machine Learning · Computer Science 2026-01-13 Suvo Banik , Troy D. Loeffler , Henry Chan , Sukriti Manna , Orcun Yildiz , Tom Peterka , Subramanian Sankaranarayanan

Graph generation is a fundamental problem in graph learning with broad applications across Web-scale systems, knowledge graphs, and scientific domains such as drug and material discovery. Recent approaches leverage diffusion models for…

Machine Learning · Computer Science 2026-03-18 Jiachi Zhao , Zehong Wang , Yamei Liao , Chuxu Zhang , Yanfang Ye

Targeted protein degradation (TPD) is a rapidly growing field in modern drug discovery that aims to regulate the intracellular levels of proteins by harnessing the cell's innate degradation pathways to selectively target and degrade…

Biomolecules · Quantitative Biology 2024-06-25 Yossra Gharbi , Rocío Mercado

De novo peptide sequencing is a critical task in proteomics. However, the performance of current deep learning-based methods is limited by the inherent complexity of mass spectrometry data and the heterogeneous distribution of noise…

Machine Learning · Computer Science 2025-06-02 Zijie Qiu , Jiaqi Wei , Xiang Zhang , Sheng Xu , Kai Zou , Zhi Jin , Zhiqiang Gao , Nanqing Dong , Siqi Sun

The design of protein sequences with desired functionalities is a fundamental task in protein engineering. Deep generative methods, such as autoregressive models and diffusion models, have greatly accelerated the discovery of novel protein…

Machine Learning · Computer Science 2025-04-16 Zitai Kong , Yiheng Zhu , Yinlong Xu , Hanjing Zhou , Mingzhe Yin , Jialu Wu , Hongxia Xu , Chang-Yu Hsieh , Tingjun Hou , Jian Wu

A multiobjective optimization method is proposed for obtaining the optimal plane trusses simultaneously for various aspect ratios of the initial ground structure as a set of Pareto optimal solutions generated through a single optimization…

Optimization and Control · Mathematics 2023-08-01 Makoto Ohsaki , Saku Aoyagi , Kazuki Hayashi

Construction of a scaffold structure that supports a desired motif, conferring protein function, shows promise for the design of vaccines and enzymes. But a general solution to this motif-scaffolding problem remains open. Current…

Biomolecules · Quantitative Biology 2023-03-21 Brian L. Trippe , Jason Yim , Doug Tischer , David Baker , Tamara Broderick , Regina Barzilay , Tommi Jaakkola

Large-scale multi-objective optimization poses challenges to existing evolutionary algorithms in maintaining the performances of convergence and diversity because of high dimensional decision variables. Inspired by the motion of particles…

Neural and Evolutionary Computing · Computer Science 2025-09-22 Jia-Cheng Li , Min-Rong Chen , Guo-Qiang Zeng , Jian Weng , Man Wang , Jia-Lin Mai

Recent studies demonstrate that diffusion planners benefit from sparse-step planning over single-step planning. Training models to skip steps in their trajectories helps capture long-term dependencies without additional memory or…

Artificial Intelligence · Computer Science 2026-04-15 Crimson Stambaugh , Rajesh P. N. Rao

The Gene or DNA sequence in every cell does not control genetic properties on its own; Rather, this is done through translation of DNA into protein and subsequent formation of a certain 3D structure. The biological function of a protein is…

Computational Engineering, Finance, and Science · Computer Science 2019-05-30 Leila Khalatbari , Mohammad Reza Kangavari , Saeid Hosseini , Hongzhi Yin , Ngai-Man Cheung

Multiobjective optimization plays an increasingly important role in modern applications, where several criteria are often of equal importance. The task in multiobjective optimization and multiobjective optimal control is therefore to…

Aligning text-to-image (T2I) diffusion models with preference optimization is valuable for human-annotated datasets, but the heavy cost of manual data collection limits scalability. Using reward models offers an alternative, however,…

Computer Vision and Pattern Recognition · Computer Science 2025-09-29 Kyungmin Lee , Xiaohang Li , Qifei Wang , Junfeng He , Junjie Ke , Ming-Hsuan Yang , Irfan Essa , Jinwoo Shin , Feng Yang , Yinxiao Li

Recent studies have demonstrated the strong empirical performance of diffusion models on discrete sequences across domains from natural language to biological sequence generation. For example, in the protein inverse folding task,…

Symbolic regression aims to discover concise, interpretable mathematical expressions that satisfy desired objectives, such as fitting data, posing a highly combinatorial optimization problem. While genetic programming has been the dominant…

Machine Learning · Computer Science 2025-09-25 Zhengyao Huang , Daniel Zhengyu Huang , Tiannan Xiao , Dina Ma , Zhenyu Ming , Hao Shi , Yuanhui Wen

The advent of deep learning has introduced efficient approaches for de novo protein sequence design, significantly improving success rates and reducing development costs compared to computational or experimental methods. However, existing…

Artificial Intelligence · Computer Science 2024-07-11 Yutong Hu , Yang Tan , Andi Han , Lirong Zheng , Liang Hong , Bingxin Zhou

While deep generative models show promise for learning inverse protein folding directly from data, the lack of publicly available structure-sequence pairings limits their generalization. Previous improvements and data augmentation efforts…

Artificial Intelligence · Computer Science 2024-07-23 Jiangbin Zheng , Stan Z. Li
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