Exploring the binding pathways of the 14-3-3 zeta : protein
Structural and free-energy profiles revealed by Hamiltonian
replica exchange molecular dynamics with distancefield distance
restraints

J 2017

Exploring the binding pathways of the 14-3-3 zeta : protein Structural and free-energy profiles revealed by Hamiltonian replica exchange molecular dynamics with distancefield distance restraints

NAGY, Gabor; C. OOSTENBRINK a Jozef HRITZ

Základní údaje

Originální název

Exploring the binding pathways of the 14-3-3 zeta : protein Structural and free-energy profiles revealed by Hamiltonian replica exchange molecular dynamics with distancefield distance restraints

Autoři

NAGY, Gabor; C. OOSTENBRINK a Jozef HRITZ

Vydání

Plos one, San Francisco, Public Library of Science, 2017, 1932-6203

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.766

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/17:00095498

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

SIMULATIONS; SITES; PHOSPHOSERINE; RECOGNITION; FORCE; NMR

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 9. 3. 2018 12:21, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

The 14-3-3 zeta protein family performs regulatory functions in eukaryotic organisms by binding to a large number of phosphorylated protein partners. Whilst the binding mode of the phosphopeptides within the primary 14-3-3 zeta binding site is well established based on the crystal structures of their complexes, little is known about the binding process itself. We present a computational study of the process by which phosphopeptides bind to the 14-3-3 zeta protein. Applying a novel scheme combining Hamiltonian replica exchange molecular dynamics and distancefield restraints allowed us to map and compare the most likely phosphopeptidebinding pathways to the 14-3-3 zeta protein. The most important structural changes to the protein and peptides involved in the binding process were identified. In order to bind phosphopeptides to the primary interaction site, the 14-3-3 zeta adopted a newly found wide-opened conformation. Based on our findings we additionally propose a secondary interaction site on the inner surface of the 14-3-3 zeta dimer, and a direct interference on the binding process by the flexible C-terminal tail. A minimalistic model was designed to allow for the efficient calculation of absolute binding affinities. Binding affinities calculated from the potential of mean force along the binding pathway are in line with the available experimental estimates for two of the studied systems.

Návaznosti

GF15-34684L, projekt VaV

Název: Efektivní výpočty volných energií a konfiguračního vzorkování protein-‐proteinových interakcí

Investor: Grantová agentura ČR, Efektivní výpočty volných energií a konfiguračního vzorkování protein-proteinových interakcí, Partnerská agentura (Rakousko)

LM2015085, projekt VaV

Název: CERIT Scientific Cloud (Akronym: CERIT-SC)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CERIT Scientific Cloud

4SGA8679, interní kód MU

Název: Structural determination of the human 14-3-3zeta in complex with a double phosphorylated human tyrosine hydroxylase 1 (Akronym: MODULATOR)

Investor: Jihomoravský kraj, Structural determination of the human 14-3-3zeta in complex with a double phosphorylated human tyrosine hydroxylase 1

Citovat

NAGY, Gabor; C. OOSTENBRINK a Jozef HRITZ. Exploring the binding pathways of the 14-3-3 zeta : protein Structural and free-energy profiles revealed by Hamiltonian replica exchange molecular dynamics with distancefield distance restraints. Plos one. San Francisco: Public Library of Science, 2017, roč. 12, č. 7, s. nestránkováno, 30 s. ISSN 1932-6203. Dostupné z: https://doi.org/10.1371/journal.pone.0180633.

@article{1408304,
   author = {Nagy, Gabor and Oostenbrink, C. and Hritz, Jozef},
   article_location = {San Francisco},
   article_number = {7},
   doi = {https://doi.org/10.1371/journal.pone.0180633},
   keywords = {SIMULATIONS; SITES; PHOSPHOSERINE; RECOGNITION; FORCE; NMR},
   language = {eng},
   issn = {1932-6203},
   journal = {Plos one},
   title = {Exploring the binding pathways of the 14-3-3 zeta : protein Structural and free-energy profiles revealed by Hamiltonian replica exchange molecular dynamics with distancefield distance restraints},
   url = {http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0180633&type=printable},
   volume = {12},
   year = {2017}
}

TY  - JOUR
ID  - 1408304
AU  - Nagy, Gabor - Oostenbrink, C. - Hritz, Jozef
PY  - 2017
TI  - Exploring the binding pathways of the 14-3-3 zeta : protein Structural and free-energy profiles revealed by Hamiltonian replica exchange molecular dynamics with distancefield distance restraints
JF  - Plos one
VL  - 12
IS  - 7
SP  - nestránkováno
EP  - nestránkováno
PB  - Public Library of Science
SN  - 19326203
KW  - SIMULATIONS
KW  - SITES
KW  - PHOSPHOSERINE
KW  - RECOGNITION
KW  - FORCE
KW  - NMR
UR  - http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0180633&type=printable
L2  - http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0180633&type=printable
N2  - The 14-3-3 zeta protein family performs regulatory functions in eukaryotic organisms by binding to a large number of phosphorylated protein partners. Whilst the binding mode of the phosphopeptides within the primary 14-3-3 zeta binding site is well established based on the crystal structures of their complexes, little is known about the binding process itself. We present a computational study of the process by which phosphopeptides bind to the 14-3-3 zeta protein. Applying a novel scheme combining Hamiltonian replica exchange molecular dynamics and distancefield restraints allowed us to map and compare the most likely phosphopeptidebinding pathways to the 14-3-3 zeta protein. The most important structural changes to the protein and peptides involved in the binding process were identified. In order to bind phosphopeptides to the primary interaction site, the 14-3-3 zeta adopted a newly found wide-opened conformation. Based on our findings we additionally propose a secondary interaction site on the inner surface of the 14-3-3 zeta dimer, and a direct interference on the binding process by the flexible C-terminal tail. A minimalistic model was designed to allow for the efficient calculation of absolute binding affinities. Binding affinities calculated from the potential of mean force along the binding pathway are in line with the available experimental estimates for two of the studied systems.
ER  -

NAGY, Gabor; C. OOSTENBRINK a Jozef HRITZ. Exploring the binding pathways of the 14-3-3 zeta : protein Structural and free-energy profiles revealed by Hamiltonian replica exchange molecular dynamics with distancefield distance restraints. \textit{Plos one}. San Francisco: Public Library of Science, 2017, roč.~12, č.~7, s.~nestránkováno, 30 s. ISSN~1932-6203. Dostupné z: https://doi.org/10.1371/journal.pone.0180633.

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