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The accurate prediction of protein-RNA binding affinity remains an unsolved problem in structural biology, limiting opportunities in understanding gene regulation and designing RNA-targeting therapeutics. A central obstacle is the…

Molecule inverse folding has been a long-standing challenge in chemistry and biology, with the potential to revolutionize drug discovery and material science. Despite specified models have been proposed for different small- or…

Artificial Intelligence · Computer Science 2024-05-30 Zhangyang Gao , Jue Wang , Cheng Tan , Lirong Wu , Yufei Huang , Siyuan Li , Zhirui Ye , Stan Z. Li

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

Protein structure prediction has reached revolutionary levels of accuracy on single structures, yet distributional modeling paradigms are needed to capture the conformational ensembles and flexibility that underlie biological function.…

Biomolecules · Quantitative Biology 2023-04-06 Bowen Jing , Ezra Erives , Peter Pao-Huang , Gabriele Corso , Bonnie Berger , Tommi Jaakkola

Consistency and reliability are crucial for conducting AI research. Many famous research fields, such as object detection, have been compared and validated with solid benchmark frameworks. After AlphaFold2, the protein folding task has…

Biomolecules · Quantitative Biology 2023-08-01 Jaemyung Lee , Kyeongtak Han , Jaehoon Kim , Hasun Yu , Youhan Lee

Machine learning applications in protein sciences have ushered in a new era for designing molecules in silico. Antibodies, which currently form the largest group of biologics in clinical use, stand to benefit greatly from this shift.…

Electrostatic interactions fundamentally govern the structure, stability, and dynamics of charged (bio)matter, yet the impact of heterogeneous and anisotropic charge distributions on the behavior of protein solutions remains elusive. Here,…

Protein structure generative models excel at predicting single protein static structures from sequence, but routinely fail to capture the correct conformational state of protein complexes, critical for protein design and induced proximity…

Machine Learning · Computer Science 2026-05-27 Alon Shtrikman , Nitzan Simchi , Michal Ran Shchory , Sagie Brodsky , Eran Seger , Kirill Pevzner

Deep learning has transformed protein design, enabling accurate structure prediction, sequence optimization, and de novo protein generation. Advances in single-chain protein structure prediction via AlphaFold2, RoseTTAFold, ESMFold, and…

Machine Learning · Computer Science 2025-02-27 Gregory W. Kyro , Tianyin Qiu , Victor S. Batista

A computational method is developed to work on an inverse equilibrium problem with an interest towards applications with protein folding. In general, we are given a set of equilibrium confgiurations and want to derive the most probable…

Biological Physics · Physics 2007-05-23 John P. Donohue

Large language models (LLMs) have significantly advanced protein representation learning. However, their capacity to interpret and design antibodies through natural language remains limited. To address this challenge, we present…

Quantitative Methods · Quantitative Biology 2026-05-21 Ling Luo , Wenbin Jiang , Hongyuan Chang , Xinkang Wang , Xushi Zhang , Yueting Xiong , Mengsha Tong , Rongshan Yu

Recent advances in diffusion models have shown remarkable potential for antibody design, yet existing approaches apply uniform generation strategies that cannot adapt to each antigen's unique requirements. Inspired by B cell affinity…

Machine Learning · Computer Science 2025-08-19 Hanqi Feng , Peng Qiu , Mengchun Zhang , Yiran Tao , You Fan , Jingtao Xu , Barnabas Poczos

AlphaFold 3 represents a transformative advancement in computational biology, enhancing protein structure prediction through novel multi-scale transformer architectures, biologically informed cross-attention mechanisms, and geometry-aware…

Biomolecules · Quantitative Biology 2025-08-27 Alireza Abbaszadeh , Armita Shahlaee

Antibody-based therapeutics-including antibody-drug conjugates (ADCs), bispecific antibodies, and novel formats-are reshaping oncology, yet key determinants of efficacy, safety, and manufacturability frequently emerge after conjugation and…

Soft Condensed Matter · Physics 2026-05-18 Alberto Ocana , Jorge R. Espinosa

Antibodies are proteins produced by the immune system that recognize and bind to specific antigens, and their 3D structures are crucial for understanding their binding mechanism and designing therapeutic interventions. The specificity of…

Machine Learning · Computer Science 2024-10-23 Jiying Zhang , Zijing Liu , Shengyuan Bai , He Cao , Yu Li , Lei Zhang

Proteins exist as a dynamic ensemble of multiple conformations, and these motions are often crucial for their functions. However, current structure prediction methods predominantly yield a single conformation, overlooking the conformational…

Biomolecules · Quantitative Biology 2025-06-18 Advaith Maddipatla , Nadav Bojan Sellam , Meital Bojan , Sanketh Vedula , Paul Schanda , Ailie Marx , Alex M. Bronstein

Accurate prediction of antibody-antigen (Ab-Ag) interfaces is critical for vaccine design, immunodiagnostics, and therapeutic antibody development. However, achieving reliable predictions from sequences alone remains a challenge. In this…

Machine Learning · Computer Science 2025-09-30 Zhang-Yu You , Jiahao Ma , Hongzong Li , Ye-Fan Hu , Jian-Dong Huang

Antibody-facilitated immune responses are central to the body's defense against pathogens, viruses, and other foreign invaders. The ability of antibodies to specifically bind and neutralize antigens is vital for maintaining immunity. Over…

Machine Learning · Computer Science 2025-06-12 Delower Hossain , Ehsan Saghapour , Kevin Song , Jake Y. Chen

Protein inverse folding-that is, predicting an amino acid sequence that will fold into the desired 3D structure-is an important problem for structure-based protein design. Machine learning based methods for inverse folding typically use…

Artificial Intelligence · Computer Science 2024-10-23 Yasha Ektefaie , Olivia Viessmann , Siddharth Narayanan , Drew Dresser , J. Mark Kim , Armen Mkrtchyan

Antibody binding site prediction plays a pivotal role in computational immunology and therapeutic antibody design. Existing sequence or structure methods rely on single-view features and fail to identify antibody-specific binding sites on…

Machine Learning · Computer Science 2025-09-12 Hongzong Li , Jiahao Ma , Zhanpeng Shi , Rui Xiao , Fanming Jin , Ye-Fan Hu , Hangjun Che , Jian-Dong Huang