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The binding complexes formed by proteins and small molecule ligands are ubiquitous and critical to life. Despite recent advancements in protein structure prediction, existing algorithms are so far unable to systematically predict the…

Quantitative Methods · Quantitative Biology 2023-04-21 Zhuoran Qiao , Weili Nie , Arash Vahdat , Thomas F. Miller , Anima Anandkumar

The AlphaFold series has transformed protein structure prediction with remarkable accuracy, often matching experimental methods. AlphaFold2, AlphaFold-Multimer, and the latest AlphaFold3 represent significant strides in predicting single…

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

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

Determining the structure of a protein has been a decades-long open question. A protein's three-dimensional structure often poses nontrivial computation costs, when classical simulation algorithms are utilized. Advances in the transformer…

Machine Learning · Computer Science 2023-10-09 Chen Dun , Qiutai Pan , Shikai Jin , Ria Stevens , Mitchell D. Miller , George N. Phillips, , Anastasios Kyrillidis

While monomer protein structure prediction tools boast impressive accuracy, the prediction of protein complex structures remains a daunting challenge in the field. This challenge is particularly pronounced in scenarios involving complexes…

Biomolecules · Quantitative Biology 2024-05-20 Xiaomin Fang , Jie Gao , Jing Hu , Lihang Liu , Yang Xue , Xiaonan Zhang , Kunrui Zhu

Protein interaction modeling is central to protein design, which has been transformed by machine learning with applications in drug discovery and beyond. In this landscape, structure-based de novo binder design is cast as either conditional…

Protein structure prediction models such as AlphaFold3 (AF3) push the frontier of biomolecular modeling by incorporating science-informed architectural changes to the transformer architecture. However, these advances come at a steep system…

Biomolecules · Quantitative Biology 2025-06-27 Hoa La , Ahan Gupta , Alex Morehead , Jianlin Cheng , Minjia Zhang

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 folding models have achieved groundbreaking results typically via a combination of integrating domain knowledge into the architectural blocks and training pipelines. Nonetheless, given the success of generative models across…

Machine Learning · Computer Science 2025-12-11 Yuyang Wang , Jiarui Lu , Navdeep Jaitly , Josh Susskind , Miguel Angel Bautista

Real-world optimization problems are often constrained by complex physical laws that limit computational scalability. These constraints are inherently tied to complex regions, and thus learning models that incorporate physical and geometric…

Machine Learning · Computer Science 2026-03-10 Yilin Wen , Yi Guo , Bo Zhao , Wei Qi , Zechun Hu , Colin Jones , Jian Sun

Recent advancements in machine learning (ML) are transforming the field of structural biology. For example, AlphaFold, a groundbreaking neural network for protein structure prediction, has been widely adopted by researchers. The…

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

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

PyMOLfold is a flexible and open-source plugin designed to seamlessly integrate AI-based protein structure prediction and visualization within the widely used PyMOL molecular graphics system. By leveraging state-of-the-art protein folding…

Biomolecules · Quantitative Biology 2025-02-04 Colby T. Ford , Samee Ullah , Dinler Amaral Antunes , Tarsis Gesteira Ferreira

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

The advent of highly accurate protein structure prediction methods has fueled an exponential expansion of the protein structure database. Consequently, there is a rising demand for rapid and precise structural homolog search. Traditional…

Biomolecules · Quantitative Biology 2023-12-01 Yuan Liu , Hong-Bin Shen

Inverse protein folding, the process of designing sequences that fold into a specific 3D structure, is crucial in bio-engineering and drug discovery. Traditional methods rely on experimentally resolved structures, but these cover only a…

Biomolecules · Quantitative Biology 2023-11-27 Igor Melnyk , Aurelie Lozano , Payel Das , Vijil Chenthamarakshan

The classic paradigm of structural biology is that the sequence of a biomolecule (protein, nucleic acid, lipid, etc) determines its conformation (shape) which determines its biological function. Protein folding programs like AlphaFold…

Biomolecules · Quantitative Biology 2026-05-05 Alessio Valentini , David Pekker , Chungwen Liang , Todd Martinez , Swagatam Mukhopadhyay

Large-scale Protein Language Models (PLMs) have improved performance in protein prediction tasks, ranging from 3D structure prediction to various function predictions. In particular, AlphaFold, a ground-breaking AI system, could potentially…

Quantitative Methods · Quantitative Biology 2022-10-18 Mingyang Hu , Fajie Yuan , Kevin K. Yang , Fusong Ju , Jin Su , Hui Wang , Fei Yang , Qiuyang Ding
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