Benchmarking of force fields to characterize the intrinsically disordered R2-FUS-LC region.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
30 08 2023
30 08 2023
Historique:
received:
26
12
2022
accepted:
16
08
2023
medline:
1
9
2023
pubmed:
31
8
2023
entrez:
30
8
2023
Statut:
epublish
Résumé
Intrinsically Disordered Proteins (IDPs) play crucial roles in numerous diseases like Alzheimer's and ALS by forming irreversible amyloid fibrils. The effectiveness of force fields (FFs) developed for globular proteins and their modified versions for IDPs varies depending on the specific protein. This study assesses 13 FFs, including AMBER and CHARMM, by simulating the R2 region of the FUS-LC domain (R2-FUS-LC region), an IDP implicated in ALS. Due to the flexibility of the region, we show that utilizing multiple measures, which evaluate the local and global conformations, and combining them together into a final score are important for a comprehensive evaluation of force fields. The results suggest c36m2021s3p with mTIP3p water model is the most balanced FF, capable of generating various conformations compatible with known ones. In addition, the mTIP3P water model is computationally more efficient than those of top-ranked AMBER FFs with four-site water models. The evaluation also reveals that AMBER FFs tend to generate more compact conformations compared to CHARMM FFs but also more non-native contacts. The top-ranking AMBER and CHARMM FFs can reproduce intra-peptide contacts but underperform for inter-peptide contacts, indicating there is room for improvement.
Identifiants
pubmed: 37648703
doi: 10.1038/s41598-023-40801-6
pii: 10.1038/s41598-023-40801-6
pmc: PMC10468508
doi:
Substances chimiques
Intrinsically Disordered Proteins
0
Water
059QF0KO0R
FUS protein, human
0
RNA-Binding Protein FUS
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14226Informations de copyright
© 2023. Springer Nature Limited.
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