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Protein structure prediction is pivotal for understanding the structure-function relationship of proteins, advancing biological research, and facilitating pharmaceutical development and experimental design. While deep learning methods and…

Machine Learning · Computer Science 2024-12-30 Kaihui Cheng , Ce Liu , Qingkun Su , Jun Wang , Liwei Zhang , Yining Tang , Yao Yao , Siyu Zhu , Yuan Qi

Predicting the effect of mutations in proteins is one of the most critical challenges in protein engineering; by knowing the effect a substitution of one (or several) residues in the protein's sequence has on its overall properties, could…

Computational Engineering, Finance, and Science · Computer Science 2020-10-08 David Medina-Ortiz , Sebastian Contreras , Juan Amado-Hinojosa , Jorge Torres-Almonacid , Juan A. Asenjo , Marcelo Navarrete , Álvaro Olivera-Nappa

For multivariate co-generation in scientific applications, we advocate pairwise block rather than joint modeling of all variables. This design mitigates the computational burden and data imbalance. To this end, we propose an Annealed…

Machine Learning · Computer Science 2026-03-10 Hantao Zhang , Jieke Wu , Mingda Xu , Xiao Hu , Yingxuan You , Pascal Fua

Despite the importance of a thermodynamically stable structure with a conserved fold for protein function, almost all evolutionary models neglect site-site correlations that arise from physical interactions between neighboring amino acid…

Populations and Evolution · Quantitative Biology 2013-12-04 Andrew J. Bordner , Hans D. Mittelmann

With the recent advances in machine learning for quantum chemistry, it is now possible to predict the chemical properties of compounds and to generate novel molecules. Existing generative models mostly use a string- or graph-based…

Biomolecules · Quantitative Biology 2020-10-14 Vitali Nesterov , Mario Wieser , Volker Roth

The discovery of inorganic crystal structures with targeted properties is a significant challenge in materials science. Generative models, especially state-of-the-art diffusion models, offer the promise of modeling complex data…

The growing significance of RNA engineering in diverse biological applications has spurred interest in developing AI methods for structure-based RNA design. While diffusion models have excelled in protein design, adapting them for RNA…

Biomolecules · Quantitative Biology 2024-06-11 Divya Nori , Wengong Jin

Quantifying the effects of amino acid mutations in proteins presents a significant challenge due to the vast combinations of residue sites and amino acid types, making experimental approaches costly and time-consuming. The Potts model has…

Methodology · Statistics 2025-05-22 Bingying Dai , Yinan Lin , Kejue Jia , Zhao Ren , Wen Zhou

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

It is the first step for understanding how RNA structure folds from base sequences that to know how its secondary structure is formed. Traditional energy-based algorithms are short of precision, particularly for non-nested sequences, while…

Quantum Physics · Physics 2023-05-18 Ji Jiang , Qipeng Yan , Ye Li , Min Lu , Ziwei Cui , Menghan Dou , Qingchun Wang , Yu-Chun Wu , Guo-Ping Guo

The observed correlations between pairs of homologous protein sequences are typically explained in terms of a Markovian dynamic of amino acid substitution. This model assumes that every location on the protein sequence has the same…

Biomolecules · Quantitative Biology 2007-05-23 Gavin E. Crooks , Steven E. Brenner

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

Nucleotide sequence variation can induce significant shifts in functional fitness. Recent nucleotide foundation models promise to predict such fitness effects directly from sequence, yet heterogeneous datasets and inconsistent preprocessing…

Genomics · Quantitative Biology 2025-11-06 Zhongmin Li , Runze Ma , Jiahao Tan , Chengzi Tan , Shuangjia Zheng

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…

Molecule generation, especially generating 3D molecular geometries from scratch (i.e., 3D \textit{de novo} generation), has become a fundamental task in drug designs. Existing diffusion-based 3D molecule generation methods could suffer from…

Machine Learning · Computer Science 2022-09-14 Lei Huang , Hengtong Zhang , Tingyang Xu , Ka-Chun Wong

The de novo design of proteins refers to creating proteins with specific structures and functions that do not naturally exist. In recent years, the accumulation of high-quality protein structure and sequence data and technological…

Biomolecules · Quantitative Biology 2025-04-24 Yujie Qin , Ming He , Changyong Yu , Ming Ni , Xian Liu , Xiaochen Bo

Neural additive model (NAM) is a recently proposed explainable artificial intelligence (XAI) method that utilizes neural network-based architectures. Given the advantages of neural networks, NAMs provide intuitive explanations for their…

Machine Learning · Computer Science 2024-11-12 Hoki Kim , Jinseong Park , Yujin Choi , Seungyun Lee , Jaewook Lee

Inverse protein folding generates valid amino acid sequences that can fold into a desired protein structure, with recent deep-learning advances showing strong potential and competitive performance. However, challenges remain, such as…

Biomolecules · Quantitative Biology 2025-07-29 Peizhen Bai , Filip Miljković , Xianyuan Liu , Leonardo De Maria , Rebecca Croasdale-Wood , Owen Rackham , Haiping Lu

Modern biomedicine is challenged to predict the effects of genetic variation. Systematic functional assays of point mutants of proteins have provided valuable empirical information, but vast regions of sequence space remain unexplored.…

Biomolecules · Quantitative Biology 2017-01-18 Thomas A. Hopf , John B. Ingraham , Frank J. Poelwijk , Michael Springer , Chris Sander , Debora S. Marks

We present a generative modeling framework for atomistic systems that combines score-based diffusion for atomic positions with a novel continuous-time discrete diffusion process for atomic types. This approach enables flexible and…

Computational Physics · Physics 2025-09-17 Nikolaj Rønne , Bjørk Hammer