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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

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

Diffusion- and flow-based generative models have recently demonstrated strong performance in protein backbone generation tasks, offering unprecedented capabilities for de novo protein design. However, while achieving notable performance in…

Machine Learning · Computer Science 2025-10-29 Liyang Xie , Haoran Zhang , Zhendong Wang , Wesley Tansey , Mingyuan Zhou

Representation learning and \emph{de novo} generation of proteins are pivotal computational biology tasks. Whilst natural language processing (NLP) techniques have proven highly effective for protein sequence modelling, structure modelling…

Quantitative Methods · Quantitative Biology 2025-01-08 Benoit Gaujac , Jérémie Donà , Liviu Copoiu , Timothy Atkinson , Thomas Pierrot , Thomas D. Barrett

Dual-target therapeutic strategies have become a compelling approach and attracted significant attention due to various benefits, such as their potential in overcoming drug resistance in cancer therapy. Considering the tremendous success…

Machine Learning · Computer Science 2024-11-27 Xiangxin Zhou , Jiaqi Guan , Yijia Zhang , Xingang Peng , Liang Wang , Jianzhu Ma

We introduce deep neural networks for the analysis of anatomical shapes that learn a low-dimensional shape representation from the given task, instead of relying on hand-engineered representations. Our framework is modular and consists of…

Computer Vision and Pattern Recognition · Computer Science 2020-10-05 Benjamin Gutierrez Becker , Ignacio Sarasua , Christian Wachinger

Recent advances in generative deep learning have transformed small molecule design, but most methods lack biological systems context, focusing narrowly on specific protein pockets. We introduce a non-differentiable diffusion guidance method…

Biomolecules · Quantitative Biology 2024-10-15 Vincent D. Zaballa , Elliot E. Hui

Autonomous materials discovery with desired properties is one of the ultimate goals for materials science, and the current studies have been focusing mostly on high-throughput screening based on density functional theory calculations and…

In the past decade, Artificial Intelligence driven drug design and discovery has been a hot research topic, where an important branch is molecule generation by generative models, from GAN-based models and VAE-based models to the latest…

Biomolecules · Quantitative Biology 2023-10-10 Siyuan Guo , Jihong Guan , Shuigeng Zhou

Deep learning is catalyzing a scientific revolution fueled by big data, accessible toolkits, and powerful computational resources, impacting many fields including protein structural modeling. Protein structural modeling, such as predicting…

Biomolecules · Quantitative Biology 2020-07-17 Wenhao Gao , Sai Pooja Mahajan , Jeremias Sulam , Jeffrey J. Gray

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…

Sequence generative models are transforming protein engineering. However, no principled framework exists for conditioning these models on auxiliary information, such as experimental data, without additional training of a generative model.…

Machine Learning · Computer Science 2026-01-19 Junhao Xiong , Ishan Gaur , Maria Lukarska , Hunter Nisonoff , Luke M. Oltrogge , David F. Savage , Jennifer Listgarten

In the present article, we propose a paradigm shift on evolving Artificial Neural Networks (ANNs) towards a new bio-inspired design that is grounded on the structural properties, interactions, and dynamics of protein networks (PNs): the…

Neural and Evolutionary Computing · Computer Science 2024-06-10 Oscar Lao , Konstantinos Zacharopoulos , Apostolos Fournaris , Rossano Schifanella , Ioannis Arapakis

Attribute extrapolation in sample generation is challenging for deep neural networks operating beyond the training distribution. We formulate a new task for extrapolation in sequence generation, focusing on natural language and proteins,…

Machine Learning · Computer Science 2021-10-27 Alvin Chan , Ali Madani , Ben Krause , Nikhil Naik

The integration of artificial intelligence (AI) in early-stage drug discovery offers unprecedented opportunities for exploring chemical space and accelerating hit-to-lead optimization. However, docking optimization in generative approaches…

Quantitative Methods · Quantitative Biology 2025-10-03 Ekaterina Podplutova , Anastasia Vepreva , Olga A. Konovalova , Vladimir Vinogradov , Dmitrii O. Shkil , Andrei Dmitrenko

We present a model, based on symmetry and geometry, for proteins. Using elementary ideas from mathematics and physics, we derive the geometries of discrete helices and sheets. We postulate a compatible solvent-mediated emergent pairwise…

Soft Condensed Matter · Physics 2023-06-21 Jayanth R. Banavar , Achille Giacometti , Trinh X. Hoang , Amos Maritan , Tatjana Škrbić

Learning meaningful protein representation is important for a variety of biological downstream tasks such as structure-based drug design. Having witnessed the success of protein sequence pretraining, pretraining for structural data which is…

Machine Learning · Computer Science 2023-02-23 Yufei Huang , Lirong Wu , Haitao Lin , Jiangbin Zheng , Ge Wang , Stan Z. Li

Generative models aim to learn the distribution of observed data by generating new instances. With the advent of neural networks, deep generative models, including variational autoencoders (VAEs), generative adversarial networks (GANs), and…

Computer Vision and Pattern Recognition · Computer Science 2023-08-29 Zifan Shi , Sida Peng , Yinghao Xu , Andreas Geiger , Yiyi Liao , Yujun Shen

Attention-based models trained on protein sequences have demonstrated incredible success at classification and generation tasks relevant for artificial intelligence-driven protein design. However, we lack a sufficient understanding of how…

Machine Learning · Computer Science 2022-06-29 Erik Nijkamp , Jeffrey Ruffolo , Eli N. Weinstein , Nikhil Naik , Ali Madani

Deep generative models open new avenues for simulating realistic genomic data while preserving privacy and addressing data accessibility constraints. While previous studies have primarily focused on generating gene expression or haplotype…

Genomics · Quantitative Biology 2025-08-14 Sihan Xie , Thierry Tribout , Didier Boichard , Blaise Hanczar , Julien Chiquet , Eric Barrey
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