Kaempf, K.; Rabdano, S. O.; Izmailov, S. A.; Groves, A.; Podkorytov, I. S.; Skrynnikov, N. R. Local and Global Dynamics of Intrinsically Disordered Proteins: A Case Study of H4 Histone Tail. The FEBS Journal 2017, 284 (Suppl. 1), 95.
DOI: 10.1111/febs.14171.
Proteins without defined secondary structure are called intrinsically disordered proteins (IDPs). While IDPs have been extensively studied over the last two decades, the relationship between spin relaxation rates measured in IDPs and their underlying motional modes remains poorly understood. To address this problem we have chosen to investigate the temperature-dependent 15N relaxation in the intrinsically disordered 26-residue N-terminal part of the histone protein H4. Experimentally, we measured 15N R1 and transverse cross-correlation rates η in a T range of 5 to 55°C. In addition, MD simulations were performed using AMBER14 with ff14SB force field and SPC/E, TIP3P, TIP4P-EW or TIP4P-D water models. We found that the latter model, which had been designed for use with IDPs, displayed consistently good agreement with the experimental data. More conventional models (SPC/E, TIP3P, TIP4P-EW) showed evidence of systematic bias toward high relaxation rates. Using the simulation data we have further confirmed that relaxation-active dynamics of the H4 peptide can be well described by a combination of two modes: a fast mode (50–300 ps) and a slow mode (1– 3 ns). Both modes are highly localized and can be attributed to torsional angle dynamics within a short segment of the peptide chain, ca. 5–8 residues. Backbone angle dynamics can be classified as harmonic fluctuations and large-amplitude jumps (i.e. transitions between different basins on the Ramachandran map). We have shown that jumps can significantly contribute to both fast and slow motional modes as detected in the H4 peptide. We conclude that a combination of temperature-dependent spin relaxation data and the recently developed specialized MD models can provide a valuable insight into conformational dynamics of an IDP.
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