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@article{1561296,
author = {Pokorná, Pavlína and Krepl, Miroslav and Bartova, E. and Šponer, Jiří},
article_location = {Washington DC},
article_number = {10},
doi = {http://dx.doi.org/10.1021/acs.jctc.9b00434},
keywords = {HETEROCHROMATIN PROTEIN-1 HP1; EXCHANGE MOLECULAR-DYNAMICS; DISORDERED PROTEINS; PEPTIDE RECOGNITION; PROTONATION STATES; PHASE-SEPARATION; SIDE-CHAIN; SIMULATIONS; BINDING; AMBER},
language = {eng},
issn = {1549-9618},
journal = {Journal of Chemical Theory and Computation},
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},
url = {https://pubs.acs.org/doi/10.1021/acs.jctc.9b00434},
volume = {15},
year = {2019}
}
TY - JOUR
ID - 1561296
AU - Pokorná, Pavlína - Krepl, Miroslav - Bartova, E. - Šponer, Jiří
PY - 2019
TI - 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
JF - Journal of Chemical Theory and Computation
VL - 15
IS - 10
SP - 5659-5673
EP - 5659-5673
PB - American Chemical Society
SN - 15499618
KW - HETEROCHROMATIN PROTEIN-1 HP1
KW - EXCHANGE MOLECULAR-DYNAMICS
KW - DISORDERED PROTEINS
KW - PEPTIDE RECOGNITION
KW - PROTONATION STATES
KW - PHASE-SEPARATION
KW - SIDE-CHAIN
KW - SIMULATIONS
KW - BINDING
KW - AMBER
UR - https://pubs.acs.org/doi/10.1021/acs.jctc.9b00434
L2 - https://pubs.acs.org/doi/10.1021/acs.jctc.9b00434
N2 - 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.
ER -
POKORNÁ, Pavlína, Miroslav KREPL, E. BARTOVA and Jiří ŠPONER. 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. \textit{Journal of Chemical Theory and Computation}. Washington DC: American Chemical Society, 2019, vol.~15, No~10, p.~5659-5673. ISSN~1549-9618. Available from: https://dx.doi.org/10.1021/acs.jctc.9b00434.
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