As a bonus, because it's a new year we have updated the Mol* viewer with fullscreen and VR support 👍 happy glycosylating 🤓😍

This ⬇️ is screenshot of the Advanced Settings I used to produce the ensemble shown in the picture above,

And a super special THANK YOU to Oracle for unparalleled support from the get-go through Oracle for Research (Rich Pitts and Mike Reilly 🙏) and now through OCI phenomenal support!

Stay tuned for a whole lot of 🔥 stuff coming up in the new year!

GlycoShape couldn't have happened without all the hard work, super skillzzz and dedication of our team, current (below) and previous members! 🤩🤩 EF is not the only cat, you can scroll over the photos to discover all others 😍 And key funding from @researchireland.ie (former SFI) FFP🙏 ⬇️🧵

We have used this approach to rebuild hyperglycosylated human EPO (or NESP shown below in the gif) in seconds 🏎️💨 as part of MSci and postgraduate summer schools structure glycoengineering for biologics workshop ⬇️🧵

We have also a new and improved Re-Glyco Ensemble, where you can see through a multiframe (50 to 500 frames from MD) glycan structure view, statistics and corresponding SASA analysis how the protein structure shifts the conformational equilibrium of the glycans ⬇️🧵

We are not only continuing to grow our library, but also continuously perfecting and expanding our tools. Re-Glyco is leading the way 🤩, with improved computational efficiency 🏎️💨 and informative queuing widget and calculation process log ⬇️🧵

To do that we built the largest OA 3D library of glycan structures worldwide 🤯, counting 882 unique glycans complemented by at least 3 conformers each to account for their dynamics, obtained from the analysis of multimicrosecond MD simulations doi.org/10.1038/s415... ⬇️🧵

Since Dec 2023 Glycoshape has progressively built a community of glycoengineers that continues to grow. These scientists recognise that to understand glycoproteins structure and function we need to take into consideration the glycans they have, with their micro and macro heterogeneity 🧵⬇️

Great to see that the authors chose to use our GAP analysis for evaluating the glycan dynamics! 🤩😻 🙏

We hope that this example, originated by our own curiosity, will inspire folks to use our tools to investigate how glycan structure impacts biological function

Also read the bioRxiv, it's awesome!

This insight does not substitute MD simulations at all, but can complement it for high throughput as it took us seconds to build the structures you see with Re-Glyco Ensemble, about 30 mins to investigate and run rotameric search, and a whole lot of time to play around with pretty pictures 🤓 ⬇️🧵

Fucosylation does not change that, but it makes the fold less compact as it sits between the a6 arm and the core. The presence of fucose in this case allows the glycan to access all its preferred conformational degrees of freedom around the pocket indicated by a circle ⬇️🧵

We see (with just 50 frames from multimicrosecond MD data available in the database) that the conformation of the non-fucosylated glycan (G44826KU) is restricted by the protein structure. Indeed, the a6 arm (esp with gal and sia) prefers to fold over the core ⬇️🧵 doi.org/10.1093/glyc...

Glycans structure and flexibility is an inherent property of their structure and branching. The conformational equilibrium is only shifted when the protein architecture requires a selection of conformers that complement it best. This appears to be one of those cases

The authors add a case study on the lymphocyte homing receptor integrin α(4)β(7) (3V4V PDB and P13612 UniProt) to complement the experiment, showing how the impact of fucosylation at N138 (N105 in the PDB) with implication to integrin function 😮 We couldn't wait to see how that works ⬇️🧵

More to the mystery, C-man is found in thrombospondin type 1 repeats (TSRs) and cytokine receptor motifs and seemingly nowhere else, where it is essential to protein folding and stability

[1] Bloch et al. Nat Chem Biol (2023) doi.org/10.1038/s415...
[2] glycopedia.eu/echapter/abs...

This unique modification is introduced by the tryptophan C-mannosyltransferase (CMT). The beautiful structure of the C elegans CMT and the reaction are described in the brilliant work of Joël Bloch and coworkers[1].

3/3 GlycoShape is an open access library of glycan structures from MD simulations that gives users all the diff structures significantly occupied at equilibrium and tools to reconstruct the target glycoproteins with a single representative conformer (Re-Glyco) or multiple (Re-Glyco Ensemble)