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Integrative modeling enables structure determination for large macromolecular assemblies by combining data from multiple sources of experiment data with theoretical and computational predictions. Recent advancements in AI-based structure…

Biomolecules · Quantitative Biology 2025-01-24 Kartik Majila , Shreyas Arvindekar , Muskaan Jindal , Shruthi Viswanath

AI-based in silico methods have improved protein structure prediction but often struggle with large protein complexes (PCs) involving multiple interacting proteins due to missing 3D spatial cues. Experimental techniques like Cryo-EM are…

Structural prediction of protein-protein interactions is important to understand the molecular basis of cellular interactions, but it still faces major challenges when significant conformational changes are present. We propose a generative…

Computational Engineering, Finance, and Science · Computer Science 2025-09-26 Rujie Yin , Yang Shen

Computational protein design is experiencing a transformation driven by AI/ML. However, the range of potential protein sequences and structures is astronomically vast, even for moderately sized proteins. Hence, achieving convergence between…

Distributed, Parallel, and Cluster Computing · Computer Science 2025-10-09 Aymen Alsaadi , Jonathan Ash , Mikhail Titov , Matteo Turilli , Andre Merzky , Shantenu Jha , Sagar Khare

Intrinsically disordered proteins and regions are increasingly appreciated for their abundance in the proteome and the many functional roles they play in the cell. In this short review, we describe a variety of approaches used to obtain…

Biological Physics · Physics 2024-12-31 Zi Hao Liu , Maria Tsanai , Oufan Zhang , Teresa Head-Gordon , Julie Forman-Kay

Protein Structure Prediction (PSP) is an unsolved problem in the field of computational biology. The problem of protein structure prediction is about predicting the native conformation of a protein, while its sequence of amino acids is…

Biomolecules · Quantitative Biology 2022-06-06 Hossein Parineh , Nasser Mozayani

Accurate protein structures are essential for understanding biological function, yet incorporating experimental data into protein generative models remains a major challenge. Most predictors of experimental observables are…

Machine Learning · Computer Science 2025-11-18 Nadav Bojan Sellam , Meital Bojan , Paul Schanda , Alex Bronstein

Small-molecule foundation models are typically pretrained on standalone molecular data, unlike vision and language models that often benefit from cross-modal or relational supervision. Protein-ligand co-folding provides a molecular analogue…

Biomolecules · Quantitative Biology 2026-05-25 Hyosoon Jang , Hyunjin Seo , Honghui Kim , Seonghyun Park , Taewon Kim , Yunhui Jang , Sungsoo Ahn

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

Generating large ensembles of candidate conformations is standard for improving biomolecular structure prediction. Yet aimless sampling is inefficient and costly, producing many redundant conformations with limited diversity, so additional…

Biomolecules · Quantitative Biology 2025-10-21 Lihang Liu , Yang Liu , Xianbin Ye , Shanzhuo Zhang , Yuxin Li , Kunrui Zhu , Yang Xue , Xiaonan Zhang , Xiaomin Fang

This review is a tutorial for scientists interested in the problem of protein structure prediction, particularly those interested in using coarse-grained molecular dynamics models that are optimized using lessons learned from the energy…

Biomolecules · Quantitative Biology 2014-01-06 N. P. Schafer , B. L. Kim , W. Zheng , P. G. Wolynes

AlphaFold3 introduces a diffusion-based architecture that elevates protein structure prediction to all-atom resolution with improved accuracy. This state-of-the-art performance has established AlphaFold3 as a foundation model for diverse…

Machine Learning · Computer Science 2026-05-19 Zhe Zhang , Yuanning Feng , Yuxuan Song , Keyue Qiu , Hao Zhou , Wei-Ying Ma

In this study, the distributions of protein structure classes (or folding types) of experimentally determined structures from a legacy dataset and a comprehensive database (SCOP) are modeled precisely with geometric constructs such as…

Biomolecules · Quantitative Biology 2025-10-21 Boryeu Mao

We present InvMSAFold, an inverse folding method for generating protein sequences that is optimized for diversity and speed. For a given structure, InvMSAFold generates the parameters of a probability distribution over the space of…

Quantitative Methods · Quantitative Biology 2025-05-30 Luca Alessandro Silva , Barthelemy Meynard-Piganeau , Carlo Lucibello , Christoph Feinauer

AI-powered drug discovery typically relies on the successful prediction of compound-protein interactions, which are pivotal for the evaluation of designed compound molecules in structure-based drug design and represent a core challenge in…

Biomolecules · Quantitative Biology 2025-04-22 Pingfei Zhu , Chenyang Zhao , Haishi Zhao , Bo Yang

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

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

Inverse Protein Folding (IPF) is a critical subtask in the field of protein design, aiming to engineer amino acid sequences capable of folding correctly into a specified three-dimensional (3D) conformation. Although substantial progress has…

Computation and Language · Computer Science 2025-05-20 Yanting Li , Jiyue Jiang , Zikang Wang , Ziqian Lin , Dongchen He , Yuheng Shan , Yanruisheng Shao , Jiayi Li , Xiangyu Shi , Jiuming Wang , Yanyu Chen , Yimin Fan , Han Li , Yu Li

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

The 2024 Nobel Prize in Chemistry was awarded in part for protein structure prediction using AlphaFold2, an artificial intelligence/machine learning (AI/ML) model trained on vast amounts of sequence and 3D structure data. AlphaFold2 and…

Biomolecules · Quantitative Biology 2025-04-22 Alexander M. Ille , Emily Anas , Michael B. Mathews , Stephen K. Burley