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Highly accurate biomolecular structure prediction is a key component of developing biomolecular foundation models, and one of the most critical aspects of building foundation models is identifying the recipes for scaling the model. In this…

Biomolecules · Quantitative Biology 2026-01-02 Yi Zhou , Chan Lu , Yiming Ma , Wei Qu , Fei Ye , Kexin Zhang , Lan Wang , Minrui Gui , Quanquan Gu

The conformational landscape of proteins is crucial to understanding their functionality in complex biological processes. Traditional physics-based computational methods, such as molecular dynamics (MD) simulations, suffer from rare event…

Biomolecules · Quantitative Biology 2024-09-25 Yan Wang , Lihao Wang , Yuning Shen , Yiqun Wang , Huizhuo Yuan , Yue Wu , Quanquan Gu

Accurate protein structure prediction can significantly accelerate the development of life science. The accuracy of AlphaFold2, a frontier end-to-end structure prediction system, is already close to that of the experimental determination…

Distributed, Parallel, and Cluster Computing · Computer Science 2022-07-14 Guoxia Wang , Xiaomin Fang , Zhihua Wu , Yiqun Liu , Yang Xue , Yingfei Xiang , Dianhai Yu , Fan Wang , Yanjun Ma

The prediction of protein 3D structure from amino acid sequence is a computational grand challenge in biophysics, and plays a key role in robust protein structure prediction algorithms, from drug discovery to genome interpretation. The…

Biomolecules · Quantitative Biology 2024-07-03 Hyun Park , Parth Patel , Roland Haas , E. A. Huerta

AI-based protein structure prediction pipelines, such as AlphaFold2, have achieved near-experimental accuracy. These advanced pipelines mainly rely on Multiple Sequence Alignments (MSAs) as inputs to learn the co-evolution information from…

Biomolecules · Quantitative Biology 2023-10-19 Xiaomin Fang , Fan Wang , Lihang Liu , Jingzhou He , Dayong Lin , Yingfei Xiang , Xiaonan Zhang , Hua Wu , Hui Li , Le Song

Generating protein sequences that fold into a intended 3D structure is a fundamental step in de novo protein design. De facto methods utilize autoregressive generation, but this eschews higher order interactions that could be exploited to…

Biomolecules · Quantitative Biology 2023-12-06 John J. Yang , Jason Yim , Regina Barzilay , Tommi Jaakkola

Data-driven predictive methods which can efficiently and accurately transform protein sequences into biologically active structures are highly valuable for scientific research and medical development. Determining accurate folding landscape…

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

Protein function relies on dynamic conformational ensembles, yet current generative models like AlphaFold3 often fail to produce ensembles that match experimental data. Recent experiment-guided generators attempt to address this by steering…

AlphaFold predicts protein structures from the amino acid sequence at or near experimental resolution, solving the 50-year-old protein folding challenge, leading to progress by transforming large-scale genomics data into protein structures.…

Biomolecules · Quantitative Biology 2021-11-16 Bozitao Zhong , Xiaoming Su , Minhua Wen , Sichen Zuo , Liang Hong , James Lin

Protein backbone generation plays a central role in de novo protein design and is significant for many biological and medical applications. Although diffusion and flow-based generative models provide potential solutions to this challenging…

Machine Learning · Computer Science 2025-05-29 Angxiao Yue , Zichong Wang , Hongteng Xu

Protein design with desirable properties has been a significant challenge for many decades. Generative artificial intelligence is a promising approach and has achieved great success in various protein generation tasks. Notably, diffusion…

Breakthroughs in high-accuracy protein structure prediction, such as AlphaFold, have established receptor-based molecule design as a critical driver for rapid early-phase drug discovery. However, most approaches still struggle to balance…

Biomolecules · Quantitative Biology 2025-06-18 Dong Xu , Zhangfan Yang , Ka-chun Wong , Zexuan Zhu , Jiangqiang Li , Junkai Ji

The recent breakthrough of AlphaFold3 in modeling complex biomolecular interactions, including those between proteins and ligands, nucleotides, or metal ions, creates new opportunities for protein design. In so-called inverse protein…

Biomolecules · Quantitative Biology 2025-07-22 Kai Yi , Kiarash Jamali , Sjors H. W. Scheres

This paper presents a novel approach for predicting the relative populations of protein conformations using AlphaFold 2, an AI-powered method that has revolutionized biology by enabling the accurate prediction of protein structures. While…

Proteins play a critical role in carrying out biological functions, and their 3D structures are essential in determining their functions. Accurately predicting the conformation of protein side-chains given their backbones is important for…

Quantitative Methods · Quantitative Biology 2024-02-19 Yangtian Zhang , Zuobai Zhang , Bozitao Zhong , Sanchit Misra , Jian Tang

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

SE(3)-based generative models have shown great promise in protein geometry modeling and effective structure design. However, the field currently lacks a modularized benchmark to enable comprehensive investigation and fair comparison of…

Machine Learning · Computer Science 2025-07-29 Lang Yu , Zhangyang Gao , Cheng Tan , Qin Chen , Jie Zhou , Liang He

AlphaFold can be used for both single-chain and multi-chain protein structure prediction, while the latter becomes extremely challenging as the number of chains increases. In this work, by taking each chain as a node and assembly actions as…

Computational Engineering, Finance, and Science · Computer Science 2024-05-08 Ziqi Gao , Tao Feng , Jiaxuan You , Chenyi Zi , Yan Zhou , Chen Zhang , Jia Li

Molecular structure generation is a fundamental problem that involves determining the 3D positions of molecules' constituents. It has crucial biological applications, such as molecular docking, protein folding, and molecular design. Recent…

Machine Learning · Computer Science 2025-08-27 Wenyin Zhou , Christopher Iliffe Sprague , Vsevolod Viliuga , Matteo Tadiello , Arne Elofsson , Hossein Azizpour