Insight into Inhibitor Binding in the Eukaryotic Proteasome: Computations of the 20S CP

A combination of molecular dynamics (MD) simulations and computational analyses uncovers structural features that may influence substrate passage and exposure to the active sites within the proteolytic chamber of the 20S proteasome core particle (CP). MD simulations of the CP reveal relaxation dynam...

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Bibliographic Details
Published in:International journal of molecular sciences 2018-12, Vol.19 (12), p.3858
Main Authors: Hodošček, Milan, Elghobashi-Meinhardt, Nadia
Format: Article
Language:English
Subjects:
active site
Cell cycle
Chambers
Computer applications
core particle (CP)
Core particles
Crystal structure
Dynamic structural analysis
electrostatic interactions
Electrostatic properties
Inhibitors
Investigations
Molecular dynamics
molecular dynamics (MD)
Peptides
proteasome
Proteasomes
Proteins
Proteolysis
proteolytic
Signal transduction
Simulation
simulations
Spectrum analysis
SyringolinA inhibitor
Viscosity
Citations: Items that this one cites
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Description
Summary:A combination of molecular dynamics (MD) simulations and computational analyses uncovers structural features that may influence substrate passage and exposure to the active sites within the proteolytic chamber of the 20S proteasome core particle (CP). MD simulations of the CP reveal relaxation dynamics in which the CP slowly contracts over the 54 ns sampling period. MD simulations of the SyringolinA (SylA) inhibitor within the proteolytic B 1 ring chamber of the CP indicate that favorable van der Waals and electrostatic interactions account for the predominant association of the inhibitor with the walls of the proteolytic chamber. The time scale required for the inhibitor to travel from the center of the proteolytic chamber to the chamber wall is on the order of 4 ns, accompanied by an average energetic stabilization of approximately -20 kcal/mol.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms19123858