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Generative machine learning models are increasingly being used to design novel proteins for therapeutic and biotechnological applications. However, the current methods mostly focus on the design of proteins with a fixed backbone structure,…

Biomolecules · Quantitative Biology 2025-03-04 Petr Kouba , Joan Planas-Iglesias , Jiri Damborsky , Jiri Sedlar , Stanislav Mazurenko , Josef Sivic

The interaction of a protein with its environment can be understood and controlled via its 3D structure. Experimental methods for protein structure determination, such as X-ray crystallography or cryogenic electron microscopy, shed light on…

Machine Learning · Computer Science 2025-04-24 Axel Levy , Eric R. Chan , Sara Fridovich-Keil , Frédéric Poitevin , Ellen D. Zhong , Gordon Wetzstein

Proteins perform their biological functions through three-dimensional structures encoded by amino acid sequences, and ligand-binding protein co-design requires models that generate sequence-structure compatible proteins under explicit…

Biomolecules · Quantitative Biology 2026-05-28 Chen Wei , Fanding Xu , Minghao Sun , Zhiyuan Liu , Lin Wang , Tianrui Jia , Yihang Zhou , Yang Zhang

After the recent ground-breaking advances in protein structure prediction, one of the remaining challenges in protein machine learning is to reliably predict distributions of structural states. Parametric models of fluctuations are…

Machine Learning · Computer Science 2024-01-25 Marloes Arts , Jes Frellsen , Wouter Boomsma

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

Proteins adopt multiple structural conformations to perform their diverse biological functions, and understanding these conformations is crucial for advancing drug discovery. Traditional physics-based simulation methods often struggle with…

Biomolecules · Quantitative Biology 2025-03-14 Jiarui Lu , Xiaoyin Chen , Stephen Zhewen Lu , Chence Shi , Hongyu Guo , Yoshua Bengio , Jian Tang

Inverse protein folding is challenging due to its inherent one-to-many mapping characteristic, where numerous possible amino acid sequences can fold into a single, identical protein backbone. This task involves not only identifying viable…

Quantitative Methods · Quantitative Biology 2023-11-08 Kai Yi , Bingxin Zhou , Yiqing Shen , Pietro Liò , Yu Guang Wang

Diffusion models have achieved remarkable success in image and video generation. In this work, we demonstrate that diffusion models can also \textit{generate high-performing neural network parameters}. Our approach is simple, utilizing an…

Machine Learning · Computer Science 2025-01-03 Kai Wang , Dongwen Tang , Boya Zeng , Yida Yin , Zhaopan Xu , Yukun Zhou , Zelin Zang , Trevor Darrell , Zhuang Liu , Yang You

Proteins perform critical processes in all living systems: converting solar energy into chemical energy, replicating DNA, as the basis of highly performant materials, sensing and much more. While an incredible range of functionality has…

Biomolecules · Quantitative Biology 2021-09-29 Leonardo V. Castorina , Rokas Petrenas , Kartic Subr , Christopher W. Wood

Protein is linked to almost every life process. Therefore, analyzing the biological structure and property of protein sequences is critical to the exploration of life, as well as disease detection and drug discovery. Traditional protein…

Machine Learning · Computer Science 2021-12-08 Yijia Xiao , Jiezhong Qiu , Ziang Li , Chang-Yu Hsieh , Jie Tang

This work presents RNAdiffusion, a latent diffusion model for generating and optimizing discrete RNA sequences of variable lengths. RNA is a key intermediary between DNA and protein, exhibiting high sequence diversity and complex…

Machine Learning · Computer Science 2024-10-03 Kaixuan Huang , Yukang Yang , Kaidi Fu , Yanyi Chu , Le Cong , Mengdi Wang

Predicting protein functional characteristics from structure remains a central problem in protein science, with broad implications from understanding the mechanisms of disease to designing novel therapeutics. Unfortunately, current machine…

Biological Physics · Physics 2024-09-30 Kevin Borisiak , Gian Marco Visani , Armita Nourmohammad

n this work, we propose a latent molecular diffusion model that can make the generated 3D molecules rich in diversity and maintain rich geometric features. The model captures the information of the forces and local constraints between atoms…

Machine Learning · Computer Science 2024-12-06 Xiang Chen

Recently, many generative models for de novo protein structure design have emerged. Yet, only few tackle the difficult task of directly generating fully atomistic structures jointly with the underlying amino acid sequence. This is…

Structure-based drug design (SBDD) aims to design small-molecule ligands that bind with high affinity and specificity to pre-determined protein targets. Generative SBDD methods leverage structural data of drugs in complex with their protein…

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

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

Recent advances in geometric deep learning and generative modeling have enabled the design of novel proteins with a wide range of desired properties. However, current state-of-the-art approaches are typically restricted to generating…

Biomolecules · Quantitative Biology 2025-08-26 Vsevolod Viliuga , Leif Seute , Nicolas Wolf , Simon Wagner , Arne Elofsson , Jan Stühmer , Frauke Gräter

Protein sequence design has seen significant advances through discrete diffusion and autoregressive approaches, yet the potential of continuous diffusion remains underexplored. Here, we present DiMA, a latent diffusion framework that…

Cryo-electron microscopy (cryo-EM) is unique among tools in structural biology in its ability to image large, dynamic protein complexes. Key to this ability is image processing algorithms for heterogeneous cryo-EM reconstruction, including…

Quantitative Methods · Quantitative Biology 2022-11-28 Karsten Kreis , Tim Dockhorn , Zihao Li , Ellen Zhong