It’s the most wonderful #glycotime of the year!!
Let us introduce you to #GlycoShape (https://glycoshape.org and #bioRxiv link below), a web platform that allows users to restore glycoproteins 3D structures (PDB, AF/RoseTTAFold or own) to their natural, functional state by adding the missing glycan structures. #bioRxiv tootorial
1/8
https://doi.org/10.1101/2023.12.11.571101
Part 2/8. The #GlycoShape glycan database (#GDB) currently counts 435 distinct glycan structures derived from 1 ms of cumulative sampling by molecular dynamics. The focus of the GDB is now on mammalian structures, yet we have examples from all species. MD trajectories are passed through the Glycan Analysis Pipeline (GAP) which outputs an ensemble of 3D structure representing the accessible conformational space.
Part 3/8. The #Re-Glyco tool in GlycoShape sources structures directly from the GDB and links them to the uploaded protein structures through a genetic algorithm. Users can upload their own PDB structures, or fetch it directly from the RCSB PDB with a PDB id, or from the AlphaFold Protein Structure Database with a UniProt id. Re-Glyco can perform all types of N- and O-glycosylation and C-mannosylation common is eukaryotes and prokaryotes.
Part 4/8. Where protein N-glycosylation is not known, #Re-Glyco can perform a GlcNAc Scanning test which reports all the potentially occupied sequons. This tool scores a 92% success rate against experimentally confirmed sites annotated in #UniProt. Moreover, the results of GlcNAc Scanning can flag flaws in the protein structure that would otherwise be impossible to discern and correct.
Part 5/8. Extensive testing with #AlphaFold structures from the EBI-EMBL database confirms earlier work indicating that predicted structures are suitable for reintroducing native glycosylation,. Here we also propose strategies to introduce modifications to the underlying proteins, where required to allow glycosylation.
Part 6/8. Ultimately, we hope that #GlycoShape through its user-friendly and intuitive interface will allow glycobiology to finally enter all aspects of scientific discovery through structure, by restoring glycoproteins to their functional state, and explicitly highlight the presence of glycans and their functions in the biology of health and disease.
Any feedback, please do not hesitate to contact us.
Part 7/8. We would like to thank first and foremost Rich Pitts and Mike Riley at ORACLE for Research for their feedback, encouragement and support,
and ORACLE for Research for generous allocation of computational resources.
GlycoShape is currently hosted by ORACLE for Research. It has been a long time coming! Thank youuuuu!
Part 8/8. We are hugely grateful to all the colleagues and friends in the FAB beta testing team
that spent some quality time on GlycoShape and gave us key feedback and encouragement, highlighted nasty bugs, and gave us great new ideas and projects for the next release.
We owe you all big style! Thank youuuuu!
@Elisa what a fabulous opening line! Great thread and piece of work too!
@gpollara thank you do much Gabriele!