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How do protein structure prediction models fold proteins? We investigate this question by tracing how ESMFold folds a beta hairpin, a prevalent structural motif. Through counterfactual interventions on model latents, we identify two…

Machine Learning · Computer Science 2026-02-10 Kevin Lu , Jannik Brinkmann , Stefan Huber , Aaron Mueller , Yonatan Belinkov , David Bau , Chris Wendler

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…

In recent years, advances in artificial intelligence (AI) have transformed structural biology, particularly protein structure prediction. Though AI-based methods, such as AlphaFold (AF), often predict single conformations of proteins with…

Biomolecules · Quantitative Biology 2024-10-22 Devlina Chakravarty , Myeongsang Lee , Lauren L. Porter

Beta-turn prediction is useful in protein function studies and experimental design. Although recent approaches using machine-learning techniques such as SVM, neural networks, and K-NN have achieved good results for beta-turn pre-diction,…

Biomolecules · Quantitative Biology 2018-08-14 Chao Fang , Yi Shang , Dong Xu

Protein mutations can significantly influence protein solubility, which results in altered protein functions and leads to various diseases. Despite of tremendous effort, machine learning prediction of protein solubility changes upon…

Biomolecules · Quantitative Biology 2023-11-06 JunJie Wee , Jiahui Chen , Kelin Xia , Guo-Wei Wei

A reduced model, which can fold both helix and sheet structures, is proposed to study the problem of protein folding. The goal of this model is to find an unbiased effective potential that has included the effects of water and at the same…

Soft Condensed Matter · Physics 2007-05-23 Nan-yow Chen

AlphaFold2 (AF) is a promising tool, but is it accurate enough to predict single mutation effects? Here, we report that the localized structural deformation between protein pairs differing by only 1-3 mutations -- as measured by the…

Stacking (or stacked generalization) is an ensemble learning method with one main distinctiveness from the rest: even though several base models are trained on the original data set, their predictions are further used as input data for one…

Machine Learning · Computer Science 2024-04-19 Ilya Ploshchik , Angelos Chatzimparmpas , Andreas Kerren

Contact-assisted protein folding has made very good progress, but two challenges remain. One is accurate contact prediction for proteins lack of many sequence homologs and the other is that time-consuming folding simulation is often needed…

Biomolecules · Quantitative Biology 2022-10-12 Jinbo Xu

Uncertainties in a structure is inevitable, which generally lead to variation in dynamic response predictions. For a complex structure, brute force Monte Carlo simulation for response variation analysis is infeasible since one single run…

Machine Learning · Statistics 2020-05-08 Kai Zhou , Jiong Tang

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…

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

Reliable evaluation of protein structure predictions remains challenging, as metrics like pLDDT capture energetic stability but often miss subtle errors such as atomic clashes or conformational traps reflecting topological frustration…

A protein's function depends critically on its conformational ensemble, a collection of energy weighted structures whose balance depends on temperature and environment. Though recent deep learning (DL) methods have substantially advanced…

Biomolecules · Quantitative Biology 2026-01-09 Myeongsang Lee , Lauren L. Porter

We present AdaFold, a model-based feedback-loop framework for optimizing folding trajectories. AdaFold extracts a particle-based representation of cloth from RGB-D images and feeds back the representation to a model predictive control to…

Robotics · Computer Science 2024-12-23 Alberta Longhini , Michael C. Welle , Zackory Erickson , Danica Kragic

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 accurate screening of candidate drug ligands against target proteins through computational approaches is of prime interest to drug development efforts. Such virtual screening depends in part on methods to predict the binding affinity…

Machine Learning · Computer Science 2024-10-22 Ho-Joon Lee , Prashant S. Emani , Mark B. Gerstein

The computer artificial intelligence system AlphaFold has recently predicted previously unknown three-dimensional structures of thousands of proteins. Focusing on the subset with high-confidence scores, we algorithmically analyze these…

Biomolecules · Quantitative Biology 2022-07-18 Maarten A. Brems , Robert Runkel , Todd O. Yeates , Peter Virnau

The inapplicability of amino acid covariation methods to small protein families has limited their use for structural annotation of whole genomes. Recently, deep learning has shown promise in allowing accurate residue-residue contact…

Biomolecules · Quantitative Biology 2019-09-10 Joe G Greener , Shaun M Kandathil , David T Jones

Recent advances in geometric deep learning and generative modeling have enabled the design of novel proteins with a wide range of desired properties. However, current state-of-the-art approaches are typically restricted to generating…

Biomolecules · Quantitative Biology 2025-08-26 Vsevolod Viliuga , Leif Seute , Nicolas Wolf , Simon Wagner , Arne Elofsson , Jan Stühmer , Frauke Gräter