BindUP-Alpha: A Webserver for Predicting DNA-and RNA-binding Proteins based on Experimental and Computational Structural Models

• Published in: Journal of molecular biology Vol. 437; no. 17; p. 169240
• Main Authors: Alexandrovich, Dina, Kagan, Shani, Mandel-Gutfreund, Yael
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.09.2025
• Subjects: Algorithms; Computational Biology - methods; DNA-binding proteins; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - metabolism; function prediction; Internet; machine learning; Models, Molecular; Protein Binding; Protein Conformation; RNA-binding proteins; RNA-Binding Proteins - chemistry; RNA-Binding Proteins - metabolism; Software; Support Vector Machine; RNA-binding proteins; function prediction; machine learning; DNA-binding proteins
• ISSN: 0022-2836; 1089-8638; 1089-8638
• DOI: 10.1016/j.jmb.2025.169240

[Display omitted] •BindUP-Alpha is a webserver for predicting DNA and RNA-binding function from experimental or predicted protein structures.•BindUP-Alpha calculates and extracts features of surface patches for both experimentally and predicted protein structures.•BindUP-Alpha implements a structure-based machine learning algorithm for nucleic acid-binding function prediction. Structural data provides important information on the proteins’ function. Recent development of advanced machine learning and artificial intelligence tools, such as AlphaFold, have led to an explosion of predicted protein structures. However, many of the computed protein models contain unstructured and disordered regions, posing challenges in protein function characterization. Here we present BindUP-Alpha, an upgraded webserver for predicting nucleic acid binding proteins. Our structure-based algorithm utilizes the electrostatic features of the protein surface and other physiochemical and structural properties extracted from the protein sequence. Using a Support Vector Machine (SVM) learning approach, BindUP-Alpha successfully predicts DNA- and RNA-binding proteins from both experimentally solved structures and predicted models. In addition, BindUP-Alpha identifies electrostatic patches on the protein’s surface that represent potential nucleic-acid binding interfaces. BindUP-Alpha is freely accessible at https://bindup.technion.ac.il, providing interactive three-dimensional visualizations and downloadable text-based results.