Publication
Title
Nanoscale insight into silk-like protein self-assembly : effect of design and number of repeat units
Author
Abstract
By means of replica exchange molecular dynamics simulations we investigate how the length of a silk-like, alternating diblock oligopeptide influences its secondary and quaternary structure. We carry out simulations for two protein sizes consisting of three and five blocks, and study the stability of a single protein, a dimer, a trimer and a tetramer. Initial configurations of our simulations are beta-roll and beta-sheet structures. We find that for the triblock the secondary and quaternary structures upto and including the tetramer are unstable: the proteins melt into random coil structures and the aggregates disassemble either completely or partially. We attribute this to the competition between conformational entropy of the proteins and the formation of hydrogen bonds and hydrophobic interactions between proteins. This is confirmed by our simulations on the pentablock proteins, where we find that, as the number of monomers in the aggregate increases, individual monomers form more hydrogen bonds whereas their solvent accessible surface area decreases. For the pentablock beta-sheet protein, the monomer and the dimer melt as well, although for the beta-roll protein only the monomer melts. For both trimers and tetramers remain stable. Apparently, for these the entropy loss of forming beta-rolls and beta-sheets is compensated for in the free-energy gain due to the hydrogen-bonding and hydrophobic interactions. We also find that the middle monomers in the trimers and tetramers are conformationally much more stable than the ones on the top and the bottom. Interestingly, the latter are more stable on the tetramer than on the trimer, suggesting that as the number of monomers increases protein-protein interactions cooperatively stabilize the assembly. According to our simulations, the beta-roll and beta-sheet aggregates must be approximately equally stable.
Language
English
Source (journal)
Physical biology
Physical biology
Publication
2018
ISSN
1478-3967 [print]
1478-3975 [online]
Volume/pages
15:6(2018), 15 p.
Article Reference
066010
ISI
000444467000001
Pubmed ID
30124438
Medium
E-only publicatie
Full text (Publisher's DOI)
Full text (open access)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 08.10.2018
Last edited 11.09.2021
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