Introducing non-enzymatic crosslinks into atomistic simulations of collagen fibrils
- Author(s)
- Guido Giannetti, Justin Pils, Frauke Gräter, Debora Monego, Christoph Dellago
- Abstract
Collagen fibrils are the primary load-bearing units of connective tissues. However, generating atomistic, simulation-ready models remains challenging due to collagen’s hierarchical organization and the diversity of its crosslinking network across tissues, ages, and metabolic states. Notably, non-enzymatic advanced glycation end-product (AGE) crosslinks—central to aging and diabetic complications—are largely absent from current atomistic fibril modelling workflows.Here, we present an extension of the ColBuilder framework to generate atomistic collagen fibril models that incorporate three representative AGE-derived crosslinks (glucosepane, pentosidine, and MOLD) alongside enzymatic crosslinks. Amber99-compatible parameters are provided and assessed against QM-optimized reference geometries using all-atom molecular dynamics (MD) simulations. As proof-of-concept, we examine the mechanical response of single D-period collagen microfibrils featuring enzymatic-only, AGE-only, and mixed crosslink patterns in molecular dynamics simulations under force, and observe that AGE crosslinks differently impact the fibril structure compared to enzymatic crosslinks. The extension to ColBuilder can aid future structure-based research on collagen aging.ColBuilder is available as an open-source Python command-line package at github.com/graeter-group/colbuilder.
- Organisation(s)
- Computational and Soft Matter Physics
- External organisation(s)
- Vienna Doctoral School in Physics, Max Planck Institute for Polymer Research
- Journal
- Bioinformatics
- Volume
- 42
- No. of pages
- 9
- ISSN
- 1367-4811
- DOI
- https://doi.org/10.1093/bioinformatics/btag409
- Publication date
- 07-2026
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 102004 Bioinformatics, 103043 Computational physics
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/a116e2ee-806f-43bd-ad02-2d618cdd3234