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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
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SYSNO ASEP 0511700 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title 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 Author(s) Pokorná, Pavlína (BFU-R) ORCID
Krepl, Miroslav (BFU-R) ORCID
Bártová, Eva (BFU-R) ORCID
Šponer, Jiří (BFU-R) RID, ORCIDNumber of authors 4 Source Title Journal of Chemical Theory and Computation . - : American Chemical Society - ISSN 1549-9618
Roč. 15, č. 10 (2019), s. 5659-5673Number of pages 15 s. Publication form Print - P Language eng - English Country US - United States Keywords heterochromatin protein-1 hp1 ; exchange molecular-dynamics ; disordered proteins ; peptide recognition ; protonation states Subject RIV BE - Theoretical Physics OECD category Atomic, molecular and chemical physics (physics of atoms and molecules including collision, interaction with radiation, magnetic resonances, Mössbauer effect) R&D Projects GA18-07384S GA ČR - Czech Science Foundation (CSF) Method of publishing Limited access Institutional support BFU-R - RVO:68081707 UT WOS 000489678700042 DOI 10.1021/acs.jctc.9b00434 Annotation 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. Workplace Institute of Biophysics Contact Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Year of Publishing 2020 Electronic address https://pubs.acs.org/doi/10.1021/acs.jctc.9b00434
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