Role of Fine Structural Dynamics in Recognition of Histone H3 by HP1 gamma(CSD) Dimer and Ability of Force Fields to Describe Their Interaction Network

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F19%3A00511700" target="_blank" >RIV/68081707:_____/19:00511700 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14310/19:00107673

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acs.jctc.9b00434" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jctc.9b00434</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jctc.9b00434" target="_blank" >10.1021/acs.jctc.9b00434</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Role of Fine Structural Dynamics in Recognition of Histone H3 by HP1 gamma(CSD) Dimer and Ability of Force Fields to Describe Their Interaction Network

Popis výsledku v původním jazyce

Human heterochromatin protein 1 (HP1) is a key factor in heterochromatin formation and maintenance. Its chromo-shadow domain (CSD) homodimerizes, and the HP1 dimer acts as a hub, transiently interacting with diverse binding partner (BP) proteins. We analyze atomistic details of interactions of the HPl gamma(CSD) dimer with one of its targets, the histone H3 N-terminal tail, using molecular dynamics (MD) simulations. The goal is to complement the available X-ray crystallography data and unravel potential dynamic effects in the molecular recognition. Our results suggest that HP1(CSD)-BP recognition involves structural dynamics of both partners, including structural communication between adjacent binding pockets that may fine-tune the sequence recognition. For example, HP1 Trp174 sidechain substates may help in distinguishing residues bound in the conserved HP1(CSD) +/- 2 hydrophobic pockets. Further, there is intricate competition between the binding of negatively charged HP1 C-terminal extension and solvent anions near the +/- 2 hydrophobic pockets, which is also influenced by the BP sequence. Phosphorylated H3 Y41 can interact with the same site. We also analyze the ability of several pair-additive force fields to describe the protein-protein interface. ff14SB and ff99SB-ILDN* provide the closest correspondence with the crystallographic model. The ffl5ipq local dynamics are somewhat less consistent with details of the experimental structure, while larger perturbations of the interface commonly occur in CHARMM36m simulations. The balance of some interactions, mainly around the anion binding site, also depends on the ion parameters. Some differences between the simulated and experimental structures are attributable to crystal packing.

Název v anglickém jazyce

Role of Fine Structural Dynamics in Recognition of Histone H3 by HP1 gamma(CSD) Dimer and Ability of Force Fields to Describe Their Interaction Network

Popis výsledku anglicky

Human heterochromatin protein 1 (HP1) is a key factor in heterochromatin formation and maintenance. Its chromo-shadow domain (CSD) homodimerizes, and the HP1 dimer acts as a hub, transiently interacting with diverse binding partner (BP) proteins. We analyze atomistic details of interactions of the HPl gamma(CSD) dimer with one of its targets, the histone H3 N-terminal tail, using molecular dynamics (MD) simulations. The goal is to complement the available X-ray crystallography data and unravel potential dynamic effects in the molecular recognition. Our results suggest that HP1(CSD)-BP recognition involves structural dynamics of both partners, including structural communication between adjacent binding pockets that may fine-tune the sequence recognition. For example, HP1 Trp174 sidechain substates may help in distinguishing residues bound in the conserved HP1(CSD) +/- 2 hydrophobic pockets. Further, there is intricate competition between the binding of negatively charged HP1 C-terminal extension and solvent anions near the +/- 2 hydrophobic pockets, which is also influenced by the BP sequence. Phosphorylated H3 Y41 can interact with the same site. We also analyze the ability of several pair-additive force fields to describe the protein-protein interface. ff14SB and ff99SB-ILDN* provide the closest correspondence with the crystallographic model. The ffl5ipq local dynamics are somewhat less consistent with details of the experimental structure, while larger perturbations of the interface commonly occur in CHARMM36m simulations. The balance of some interactions, mainly around the anion binding site, also depends on the ion parameters. Some differences between the simulated and experimental structures are attributable to crystal packing.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10301 - Atomic, molecular and chemical physics (physics of atoms and molecules including collision, interaction with radiation, magnetic resonances, Mössbauer effect)

Projekt

<a href="/cs/project/GA18-07384S" target="_blank" >GA18-07384S: Od konformace po biologické funkce proteinu HP1</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Chemical Theory and Computation

ISSN

1549-9618

e-ISSN

—

Svazek periodika

15

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

5659-5673

Kód UT WoS článku

000489678700042

EID výsledku v databázi Scopus

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