Nanoscale insight into silk-like protein self-assembly: effect of design and number of repeat units

J. Razzokov, M. Naderi, P.P.A.M. van der Schoot

Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

Uittreksel

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 β-roll and β-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 β-sheet protein, the monomer and the dimer melt as well, although for the β-roll protein only the monomer melts. For both trimers and tetramers remain stable. Apparently, for these the entropy loss of forming β-rolls and β-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 β-roll and β-sheet aggregates must be approximately equally stable.
TaalEngels
Artikelnummer066010
Aantal pagina's15
TijdschriftPhysical Biology
Volume15
Nummer van het tijdschrift6
DOI's
StatusGepubliceerd - 12 sep 2018

Vingerafdruk

Silk
Proteins
Entropy
Hydrophobic and Hydrophilic Interactions
Hydrogen
Oligopeptides
Molecular Dynamics Simulation
Hydrogen Bonding

Citeer dit

@article{4400b5c8bf554a8ab6f30f24de566328,
title = "Nanoscale insight into silk-like protein self-assembly: effect of design and number of repeat units",
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 β-roll and β-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 β-sheet protein, the monomer and the dimer melt as well, although for the β-roll protein only the monomer melts. For both trimers and tetramers remain stable. Apparently, for these the entropy loss of forming β-rolls and β-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 β-roll and β-sheet aggregates must be approximately equally stable.",
author = "J. Razzokov and M. Naderi and {van der Schoot}, P.P.A.M.",
year = "2018",
month = "9",
day = "12",
doi = "10.1088/1478-3975/aadb5e",
language = "English",
volume = "15",
journal = "Physical Biology",
issn = "1478-3975",
publisher = "Institute of Physics",
number = "6",

}

Nanoscale insight into silk-like protein self-assembly: effect of design and number of repeat units. / Razzokov, J.; Naderi, M.; van der Schoot, P.P.A.M.

In: Physical Biology, Vol. 15, Nr. 6, 066010, 12.09.2018.

Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

TY - JOUR

T1 - Nanoscale insight into silk-like protein self-assembly: effect of design and number of repeat units

AU - Razzokov,J.

AU - Naderi,M.

AU - van der Schoot,P.P.A.M.

PY - 2018/9/12

Y1 - 2018/9/12

N2 - 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 β-roll and β-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 β-sheet protein, the monomer and the dimer melt as well, although for the β-roll protein only the monomer melts. For both trimers and tetramers remain stable. Apparently, for these the entropy loss of forming β-rolls and β-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 β-roll and β-sheet aggregates must be approximately equally stable.

AB - 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 β-roll and β-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 β-sheet protein, the monomer and the dimer melt as well, although for the β-roll protein only the monomer melts. For both trimers and tetramers remain stable. Apparently, for these the entropy loss of forming β-rolls and β-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 β-roll and β-sheet aggregates must be approximately equally stable.

U2 - 10.1088/1478-3975/aadb5e

DO - 10.1088/1478-3975/aadb5e

M3 - Article

VL - 15

JO - Physical Biology

T2 - Physical Biology

JF - Physical Biology

SN - 1478-3975

IS - 6

M1 - 066010

ER -