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GTcomplex: Spatial indexing-powered search and alignment of macromolecular complexes

Margelevicius, M.

2025-12-17 bioinformatics
10.64898/2025.12.15.694356 bioRxiv
Show abstract

Structural alignment of macromolecular complexes is essential for understanding their function and evolution, yet existing methods often rely on aligning individual chains before inferring complex-level correspondences, leading to inaccuracies and inefficiencies. Here we present GTcomplex, a novel algorithm that employs spatial indexing to perform holistic complex-level alignment, directly deriving chain assignments from optimal global superpositions. Benchmarking on diverse datasets--including protein complexes, viral capsids, and nucleic acid complexes--demonstrates that GTcomplex achieves state-of-the-art accuracy with substantial speed improvements over current methods. These advances enable scalable, accurate comparison of compositionally diverse and large assemblies, facilitating structural annotation, evolutionary studies, and multimeric structure prediction. GTcomplex is available as a user-friendly software package and as a web service supporting high-throughput searches.

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