Structome: a tool for the rapid assembly of datasets for structural phylogenetics

• Main Authors: Malik, Ashar J., Langer, Desiree, Verma, Chandra Shekhar, Poole, Anthony M., Allison, Jane R.
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2024
• Subjects: Medicine, Health and Life Sciences; Protein structures; Datasets
• Online Access: https://hdl.handle.net/10356/173974
• Institution: Nanyang Technological University

Protein structures carry signal of common ancestry and can therefore aid in reconstructing their evolutionary histories. To expedite the structure-informed inference process, a web server, Structome, has been developed that allows users to rapidly identify protein structures similar to a query protein and to assemble datasets useful for structure-based phylogenetics. Structome was created by clustering ∼94% of the structures in RCSB PDB using 90% sequence identity and representing each cluster by a centroid structure. Structure similarity between centroid proteins was calculated, and annotations from PDB, SCOP, and CATH were integrated. To illustrate utility, an H3 histone was used as a query, and results show that the protein structures returned by Structome span both sequence and structural diversity of the histone fold. Additionally, the pre-computed nexus-formatted distance matrix, provided by Structome, enables analysis of evolutionary relationships between proteins not identifiable using searches based on sequence similarity alone. Our results demonstrate that, beginning with a single structure, Structome can be used to rapidly generate a dataset of structural neighbours and allows deep evolutionary history of proteins to be studied.