Abstract
Coarse-grained molecular dynamics simulations are a useful tool to determine conformational ensembles of proteins. Here, we show that the coarse-grained force field Martini 3 underestimates the global dimensions of intrinsically disordered proteins (IDPs) and multidomain proteins when compared with small-angle X-ray scattering (SAXS) data and that increasing the strength of protein-water interactions favors more expanded conformations. We find that increasing the strength of interactions between protein and water by ca. 10% results in improved agreement with the SAXS data for IDPs and multidomain proteins. We also show that this correction results in a more accurate description of self-association of IDPs and folded proteins and better agreement with paramagnetic relaxation enhancement data for most IDPs. While simulations with this revised force field still show deviations to experiments for some systems, our results suggest that it is overall a substantial improvement for coarse-grained simulations of soluble proteins.
Originalsprog | Engelsk |
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Tidsskrift | Journal of Chemical Theory and Computation |
Vol/bind | 18 |
Udgave nummer | 4 |
Sider (fra-til) | 2033-2041 |
Antal sider | 9 |
ISSN | 1549-9618 |
DOI | |
Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:We thank Simone Orioli, Thea K. Schulze, Andreas Haahr Larsen, and Yong Wang for useful discussions and suggestions. We acknowledge the use of computational resources from Computerome 2.0 and the core facility for biocomputing at the Department of Biology. This research was supported by the Lundbeck Foundation BRAINSTRUC initiative (R155-2015-2666 to K.L.-L.).
Publisher Copyright:
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