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Proteins are essential macromolecules defined by their amino acid sequences, which determine their three-dimensional structures and, consequently, their functions in all living organisms. Therefore, generative protein modeling necessitates…

Machine Learning · Computer Science 2024-10-18 Xinyou Wang , Zaixiang Zheng , Fei Ye , Dongyu Xue , Shujian Huang , Quanquan Gu

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

Diffusion-based generative models have reformed generative AI, and also enabled new capabilities in the science domain, e.g., fast generation of 3D structures of molecules. In such tasks, there is often a symmetry in the system, identifying…

Machine Learning · Computer Science 2026-05-15 Yixian Xu , Yusong Wang , Shengjie Luo , Kaiyuan Gao , Tianyu He , Di He , Chang Liu

Diffusion Models (DMs) have demonstrated state-of-the-art performance in content generation without requiring adversarial training. These models are trained using a two-step process. First, a forward - diffusion - process gradually adds…

Computer Vision and Pattern Recognition · Computer Science 2024-03-13 Anwaar Ulhaq , Naveed Akhtar

Recent methods for molecular generation face a trade-off: they either enforce strict equivariance with costly architectures or relax it to gain scalability and flexibility. We propose a frame-based diffusion paradigm that achieves…

Machine Learning · Computer Science 2025-10-07 Mohan Guo , Cong Liu , Patrick Forré

Denoising diffusion probabilistic models (DDPM) are a class of generative models which have recently been shown to produce excellent samples. We show that with a few simple modifications, DDPMs can also achieve competitive log-likelihoods…

Machine Learning · Computer Science 2021-02-22 Alex Nichol , Prafulla Dhariwal

This report presents the comprehensive implementation, evaluation, and optimization of Denoising Diffusion Probabilistic Models (DDPMs) and Denoising Diffusion Implicit Models (DDIMs), which are state-of-the-art generative models. During…

Computer Vision and Pattern Recognition · Computer Science 2024-12-20 Jaineet Shah , Michael Gromis , Rickston Pinto

Structure-based drug design (SBDD) aims to generate 3D ligand molecules that bind to specific protein targets. Existing 3D deep generative models including diffusion models have shown great promise for SBDD. However, it is complex to…

Biomolecules · Quantitative Biology 2024-03-01 Zhilin Huang , Ling Yang , Zaixi Zhang , Xiangxin Zhou , Yu Bao , Xiawu Zheng , Yuwei Yang , Yu Wang , Wenming Yang

Understanding how proteins structurally interact is crucial to modern biology, with applications in drug discovery and protein design. Recent machine learning methods have formulated protein-small molecule docking as a generative problem…

Uncovering the mechanisms behind long-term memory is one of the most fascinating open problems in neuroscience and artificial intelligence. Artificial associative memory networks have been used to formalize important aspects of biological…

Machine Learning · Statistics 2023-11-20 Luca Ambrogioni

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

A popular approach to protein design is to combine a generative model with a discriminative model for conditional sampling. The generative model samples plausible sequences while the discriminative model guides a search for sequences with…

Computational protein design facilitates discovery of novel proteins with prescribed structure and functionality. Exciting designs were recently reported using novel data-driven methodologies that can be roughly divided into two categories:…

Biological Physics · Physics 2023-03-28 Cyril Malbranke , David Bikard , Simona Cocco , Rémi Monasson , Jérôme Tubiana

A diffusion probabilistic model (DPM), which constructs a forward diffusion process by gradually adding noise to data points and learns the reverse denoising process to generate new samples, has been shown to handle complex data…

Computer Vision and Pattern Recognition · Computer Science 2023-10-16 Zhengxiong Luo , Dayou Chen , Yingya Zhang , Yan Huang , Liang Wang , Yujun Shen , Deli Zhao , Jingren Zhou , Tieniu Tan

The task of deducing three-dimensional molecular configurations from their two-dimensional graph representations holds paramount importance in the fields of computational chemistry and pharmaceutical development. The rapid advancement of…

Biomolecules · Quantitative Biology 2025-01-09 Bobin Yang , Jie Deng , Zhenghan Chen , Ruoxue Wu

Antibody therapeutics are among the most successful modern medicines, yet computationally designing antibodies with desirable binding and developability properties remains challenging. While protein language models (pLMs) have emerged as…

Machine Learning · Computer Science 2026-05-11 Justin Sanders , Luca Giancardo , Lan Guo , Yue Zhao , Kemal Sonmez , Nina Cheng , Melih Yilmaz

Generating molecules that bind to specific protein targets via diffusion models has shown good promise for structure-based drug design and molecule optimization. Especially, the diffusion models with binding interaction guidance enables…

Machine Learning · Computer Science 2025-05-12 Anjie Qiao , Hao Zhang , Qianmu Yuan , Qirui Deng , Jingtian Su , Weifeng Huang , Huihao Zhou , Guo-Bo Li , Zhen Wang , Jinping Lei

Recent advances in generative artificial intelligence (AI) technologies have been significantly driven by models such as generative adversarial networks (GANs), variational autoencoders (VAEs), and denoising diffusion probabilistic models…

Machine Learning · Computer Science 2024-10-24 Chengyuan Li , Tianyu Zhang , Xusheng Du , Ye Zhang , Haoran Xie

Protein engineering is experiencing a paradigmatic shift through the integration of geometric deep learning into computational design workflows. While traditional strategies, such as rational design and directed evolution, have enabled…

Since its foundations, more than one hundred years ago, the field of structural biology has strived to understand and analyze the properties of molecules and their interactions by studying the structure that they take in 3D space. However,…

Biomolecules · Quantitative Biology 2023-02-27 Gabriele Corso
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