## Generating a conformational landscape of ubiquitin chains at atomistic resolution by back-mapping based sampling

2023
Journal article
Published
##### Published in
Frontiers in Chemistry ; 10 (2023). - 1087963. - Frontiers Research Foundation. - eISSN 2296-2646
##### Abstract
Ubiquitin chains are flexible multidomain proteins that have important biological functions in cellular signalling. Computational studies with all-atom molecular dynamics simulations of the conformational spaces of polyubiquitins can be challenging due to the system size and a multitude of long-lived meta-stable states. Coarse graining is an efficient approach to overcome this problem—at the cost of losing high-resolution details. Recently, we proposed the back-mapping based sampling (BMBS) approach that reintroduces atomistic information into a given coarse grained (CG) sampling based on a two-dimensional (2D) projection of the conformational landscape, produces an atomistic ensemble and allows to systematically compare the ensembles at the two levels of resolution. Here, we apply BMBS to K48-linked tri-ubiquitin, showing its applicability to larger systems than those it was originally introduced on and demonstrating that the algorithm scales very well with system size. In an extension of the original BMBS we test three different seeding strategies, i.e. different approaches from where in the CG landscape atomistic trajectories are initiated. Furthermore, we apply a recently introduced conformational clustering algorithm to the back-mapped atomistic ensemble. Thus, we obtain insight into the structural composition of the 2D landscape and illustrate that the dimensionality reduction algorithm separates different conformational characteristics very well into different regions of the map. This cluster analysis allows us to show how atomistic trajectories sample conformational states, move through the projection space and in sum converge to an atomistic conformational landscape that slightly differs from the original CG map, indicating a correction of flaws in the CG template.
540 Chemistry
##### Keywords
molecular dynamics simulations, dimensionality reduction, back-mapping, coarse graining, clustering, ubiquitin, polyubiquitin
##### Cite This
ISO 690HUNKLER, Simon, Teresa BUHL, Oleksandra KUKHARENKO, Christine PETER, 2023. Generating a conformational landscape of ubiquitin chains at atomistic resolution by back-mapping based sampling. In: Frontiers in Chemistry. Frontiers Research Foundation. 10, 1087963. eISSN 2296-2646. Available under: doi: 10.3389/fchem.2022.1087963
BibTex
@article{Hunkler2023-01-10Gener-59951,
year={2023},
doi={10.3389/fchem.2022.1087963},
title={Generating a conformational landscape of ubiquitin chains at atomistic resolution by back-mapping based sampling},
volume={10},
journal={Frontiers in Chemistry},
author={Hunkler, Simon and Buhl, Teresa and Kukharenko, Oleksandra and Peter, Christine},
note={DFG-Förderung: CRC 969, Grant INST 35/1134-1 FUGG Article Number: 1087963}
}

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##### Comment on publication
DFG-Förderung: CRC 969, Grant INST 35/1134-1 FUGG
Yes
Yes