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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

Generative modeling has become a central paradigm in protein research, extending machine learning beyond structure prediction toward sequence design, backbone generation, inverse folding, and biomolecular interaction modeling. However, the…

Machine Learning · Computer Science 2026-03-30 Senura Hansaja Wanasekara , Minh-Duong Nguyen , Xiaochen Liu , Nguyen H. Tran , Ken-Tye Yong

Much scientific enquiry across disciplines is founded upon a mechanistic treatment of dynamic systems that ties form to function. A highly visible instance of this is in molecular biology, where an important goal is to determine…

Biomolecules · Quantitative Biology 2021-06-17 Xiaojie Guo , Yuanqi Du , Sivani Tadepalli , Liang Zhao , Amarda Shehu

Generating molecules that bind to specific proteins is an important but challenging task in drug discovery. Previous works usually generate atoms in an auto-regressive way, where element types and 3D coordinates of atoms are generated one…

Biomolecules · Quantitative Biology 2024-07-16 Haitao Lin , Yufei Huang , Odin Zhang , Siqi Ma , Meng Liu , Xuanjing Li , Lirong Wu , Jishui Wang , Tingjun Hou , Stan Z. Li

Protein structure prediction and folding are fundamental to understanding biology, with recent deep learning advances reshaping the field. Diffusion-based generative models have revolutionized protein design, enabling the creation of novel…

Machine Learning · Computer Science 2025-10-01 Yogesh Verma , Markus Heinonen , Vikas Garg

The goal of structure-based drug discovery is to find small molecules that bind to a given target protein. Deep learning has been used to generate drug-like molecules with certain cheminformatic properties, but has not yet been applied to…

Quantitative Methods · Quantitative Biology 2022-01-27 Matthew Ragoza , Tomohide Masuda , David Ryan Koes

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

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

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

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

Proteins are macromolecules that mediate a significant fraction of the cellular processes that underlie life. An important task in bioengineering is designing proteins with specific 3D structures and chemical properties which enable…

Quantitative Methods · Quantitative Biology 2022-05-31 Namrata Anand , Tudor Achim

Proteins are the fundamental macromolecules that play diverse and crucial roles in all living matter and have tremendous implications in healthcare, manufacturing, and biotechnology. Their functions are largely determined by the sequences…

Biomolecules · Quantitative Biology 2024-09-17 Boqiao Lai

Recent advances in diffusion models have shown remarkable potential in the conditional generation of novel molecules. These models can be guided in two ways: (i) explicitly, through additional features representing the condition, or (ii)…

Machine Learning · Computer Science 2025-03-12 Yuchen Shen , Chenhao Zhang , Sijie Fu , Chenghui Zhou , Newell Washburn , Barnabás Póczos

Although machine learning has been successfully used to propose novel molecules that satisfy desired properties, it is still challenging to explore a large chemical space efficiently. In this paper, we present a conditional molecular design…

Machine Learning · Computer Science 2019-04-02 Seokho Kang , Kyunghyun Cho

Excitement at the prospect of using data-driven generative models to sample configurational ensembles of biomolecular systems stems from the extraordinary success of these models on a diverse set of high-dimensional sampling tasks. Unlike…

Statistical Mechanics · Physics 2024-02-06 Shriram Chennakesavalu , Grant M. Rotskoff

Generative models have the potential to accelerate key steps in the discovery of novel molecular therapeutics and materials. Diffusion models have recently emerged as a powerful approach, excelling at unconditional sample generation and,…

Biomolecules · Quantitative Biology 2024-07-17 Leo Klarner , Tim G. J. Rudner , Garrett M. Morris , Charlotte M. Deane , Yee Whye Teh

Proteins power a vast array of functional processes in living cells. The capability to create new proteins with designed structures and functions would thus enable the engineering of cellular behavior and development of protein-based…

Biomolecules · Quantitative Biology 2023-06-08 Yeqing Lin , Mohammed AlQuraishi

Molecular transitions -- such as protein folding, allostery, and membrane transport -- are central to biology yet remain notoriously difficult to simulate. Their intrinsic rarity pushes them beyond reach of standard molecular dynamics,…

This article makes discrete masked models for the generative modeling of discrete data controllable. The goal is to generate samples of a discrete random variable that adheres to a posterior distribution, satisfies specific constraints, or…

Machine Learning · Computer Science 2024-10-04 Wei Guo , Yuchen Zhu , Molei Tao , Yongxin Chen

Advances in deep generative models shed light on de novo molecule generation with desired properties. However, molecule generation targeted for dual protein targets still faces formidable challenges including protein 3D structure data…

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