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Exploring the trigger sequence of the GCN4 coiled‐coil: Biased molecular dynamics resolves apparent inconsistencies in NMR measurements
Author(s) -
Missimer John H.,
Dolenc Jožica,
Steinmetz Michel O.,
van Gunsteren Wilfred F.
Publication year - 2010
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.528
Subject(s) - molecular dynamics , coiled coil , sequence (biology) , nuclear magnetic resonance spectroscopy , nuclear overhauser effect , coupling constant , monomer , chemistry , j coupling , chemical physics , coupling (piping) , two dimensional nuclear magnetic resonance spectroscopy , observable , crystallography , biological system , physics , nuclear magnetic resonance , materials science , computational chemistry , biology , polymer , biochemistry , particle physics , quantum mechanics , metallurgy
Trigger sequences are indispensable elements for coiled‐coil formation. The monomeric helical trigger sequence of the yeast transcriptional activator GCN4 has been investigated recently using several solution NMR observables including nuclear Overhauser enhancement (NOE) intensities and 3 J(H N, H Cα )‐coupling constants, and a set of 20 model structures was proposed. Constrained to satisfy the NOE‐derived distance bounds, the NMR model structures do not appear to reproduce all the measured 3 J(H N ‐H Cα )‐coupling constant values, indicating that the α‐helical propensity is not uniform along the GCN4 trigger sequence. A recent methodological study of unrestrained and restrained molecular dynamics (MD) simulations of the GCN4 trigger sequence in solution showed that only MD simulations incorporating time‐averaged NOE distance restraints and instantaneous or local‐elevation 3 J‐coupling restraints could satisfy the entire set of the experimental data. In this report, we assess by means of cluster analyses the model structures characteristic of the two simulations that are compatible with the measured data and compare them with the proposed 20 NMR model structures. Striking characteristics of the MD model structures are the variability of the simulated configurations and the indication of entropic stability mediated by the aromatic N‐terminal residues 17Tyr and 18His, which are absent in the set of NMR model structures.