Structome-AlignViewer: On Confidence Assessment in Structure-Aware Alignments

Ashar J. Malik,  Siying Mao, Philip  Hugenholtz,  and  David B. Ascher

Welcome to Structome-AlignViewer

Structome-AlignViewer is an interactive web application designed to overlay 3Di character alignments onto molecular structures, enabling researchers to visually inspect alignment quality in a structural context. Given a set of protein structures, the app generates a 3Di-based multiple sequence alignment (MSA) and allows users to map alignment positions onto 3D structures. This serves as a critical sanity check, ensuring that structurally equivalent residues align properly, reducing errors that could impact downstream phylogenetic analysis, homology detection, or machine learning models. Users can click on alignment positions to highlight corresponding residues in the molecular viewer, making it easy to spot potential misalignments. Additionally, the app provides downloadable alignment files, including the full 3Di alignment and a trimmed version, where only columns with ≥50% non-gap characters are retained—ensuring a more reliable dataset for further analysis. By integrating alignment visualization with structural context, Structome-AlignViewer helps researchers validate, refine, and improve structural alignments, ultimately enhancing the accuracy of evolutionary inference and comparative structural analyses.

Start with a set of structures you would like to compare (e.g., 1hv4_A;1hv4_B;1hv4_C).


Future releases will support predicted structures and custom substitution matrices.
Description of the image

Figure: An example result showing comparison between three protein structures (RCSB PDB accession 1hv4, chain A, 1hv4, chain B, and 1hv4, chain C). The page comprises an interactive protein structure viewer (top left), an interactive protein 3Di alignment browser (bottom) and a alignment dendrogram. The dropdown "Select Structure" allows users to toggle between the compared structures. Download button allows users to download the alignment both raw and trimmed. Clicking individual columns in the alignment viewer, highlights corresponding structures in the viewer. Residues in the structure are colour coded according to their confidence values, and these modified structures can also be downloaded.