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SiteContext: A Web Server for Protein Binding Site Comparison
Journal article   Peer reviewed

SiteContext: A Web Server for Protein Binding Site Comparison

Hiba Bhatti, Jiadong Yu and Rahul Singh
Journal of molecular biology, 169791
04/02/2026
DOI: 10.1016/j.jmb.2026.169791
PMID: 41935663

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Abstract

SiteContext is a web server for comparing protein binding sites. Accurate binding site comparison is important both in structural biology and drug discovery. Extant methods typically require installation or provide coarse alignments, such as between the alpha-carbons only. Given two binding sites, SiteContext provides detailed atom-level correspondences between all the solvent-accessible surface atoms. In it, each binding site atom is encoded as a set of spherical histograms, capturing spatial distributions of other atoms in its neighborhood. A computationally efficient approximation of the Earth Mover's Distance is used to compute a transportation-based similarity score between these distributions to determine binding site similarity. Benchmarking studies shows that SiteContext is comparable to state-of-the-art methods. Its outputs include site similarity scores, atom-to-atom correspondences, and root-mean-square deviations between atoms. Correspondences are visualized and are available as downloadable files, with each atom labeled by element and parent residue. SiteContext is available at: https://tintin.cs.uiowa.edu/SiteContext/.
Structural Biology Computational Biology Transportation distance Binding site comparison

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