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

Result code in 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>

Alternative codes found

RIV/00216224:14310/19:00107673

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

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

Project

<a href="/en/project/GA18-07384S" target="_blank" >GA18-07384S: From conformation to biological functions of HP1 protein</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

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

Name of the periodical

Journal of Chemical Theory and Computation

ISSN

1549-9618

e-ISSN

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Volume of the periodical

15

Issue of the periodical within the volume

10

Country of publishing house

US - UNITED STATES

Number of pages

15

Pages from-to

5659-5673

UT code for WoS article

000489678700042

EID of the result in the Scopus database

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