Journal
BIOMOLECULES
Volume 12, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/biom12081140
Keywords
peptide aggregation; molecular dynamics; replica exchange; UNRES model
Categories
Funding
- National Science Centre [UMO-2021/40/Q/ST4/00035, UMO-2017/26/M/ST4/00044, UMO-2012/07/N/ST5/00249]
Ask authors/readers for more resources
The UNited RESidue (UNRES) model was used to study the aggregation behavior of 20 peptides with different lengths. The majority of peptides showed inter-strand beta-sheet formation, except for glutamine- and asparagine-rich peptides, which require modification of the UNRES model.
The UNited RESidue (UNRES) model of polypeptide chains was applied to study the association of 20 peptides with sizes ranging from 6 to 32 amino-acid residues. Twelve of those were potentially aggregating hexa- or heptapeptides excised from larger proteins, while the remaining eight contained potentially aggregating sequences, functionalized by attaching larger ends rich in charged residues. For 13 peptides, the experimental data of aggregation were used. The remaining seven were synthesized, and their properties were measured in this work. Multiplexed replica-exchange simulations of eight-chain systems were conducted at 12 temperatures from 260 to 370 K at concentrations from 0.421 to 5.78 mM, corresponding to the experimental conditions. The temperature profiles of the fractions of monomers and octamers showed a clear transition corresponding to aggregate dissociation. Low simulated transition temperatures were obtained for the peptides, which did not precipitate after incubation, as well as for the H-GNNQQNY-NH2 prion-protein fragment, which forms small fibrils. A substantial amount of inter-strand beta-sheets was found in most of the systems. The results suggest that UNRES simulations can be used to assess peptide aggregation except for glutamine- and asparagine-rich peptides, for which a revision of the UNRES sidechain-sidechain interaction potentials appears necessary.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available