Research ArticleChemistry

Solvent-dependent segmental dynamics in intrinsically disordered proteins

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Science Advances  28 Jun 2019:
Vol. 5, no. 6, eaax2348
DOI: 10.1126/sciadv.aax2348
  • Fig. 1 Comparison of experimental and simulated NMR relaxation rates at 278 to 298 K.

    (A) Experimental 15N transverse spin relaxation rates R2 (gray bars) measured on Ntail at different magnetic fields (columns) and temperatures (rows) are compared with the results of simulations C3P (blue line), C4P (orange), and A4P (purple). At all temperatures and fields, simulations in TIP4P/2005 capture the dynamics of Ntail better than simulations in TIP3P water (RMSD given in figs. S4 to S6). All rates are reported in s−1. Rates at 950 MHz are not shown in the interests of space. (B) Experimental 15N longitudinal spin relaxation rates (R1) measured on Ntail at different magnetic fields (columns) and temperatures (rows) [color code as in (A)]. All simulations reproduce, at least qualitatively, the sequence dependence of R2 rates, although simulations are more accurate at room temperature than at lower temperature. All rates are reported in s−1. (C) Experimental 15N{1H} steady-state NOEs measured on Ntail at different magnetic fields (columns) and temperatures (rows) [color code as in (A)]. Simulations in TIP4P/2005 reproduce the experimental values better than C3P, at all temperatures and at all fields (RMSD given in figs. S4 to S6).

  • Fig. 2 Average time scales resulted from fitting segmental dynamics correlation functions in C3P (blue), C4P (orange), and A4P (purple).

  • Fig. 3 Illustration of inter- and intrasegment dynamics contributing to NMR relaxation.

    (A) We consider a time-dependent gyration tensor for each segment (here represented by an ellipsoid), as defined in (36). The gyration tensor is diagonalized by a rotation matrix expressed as a function of time-dependent angles θ and φ that are used to compute a correlation function that reports on the time fluctuations of the orientation of the segment in the laboratory frame. (B) In the model presented in (30), all the information regarding segmental motions is encoded in the relative orientation of peptide planes. We label α1, α2 … αn the n = N(N − 1)/2 time-dependent angles identified by two Cα-Cα vectors in a segment of N residues. We compute n correlation functions reporting on intrasegment dynamics.

  • Fig. 4 Comparison of intrasegment dynamics and longest relaxation active time scale.

    Time scales associated with intrasegment dynamics at 298 K (red circles) in C3P (top), C4P (middle), and A4P (bottom) are compared with the longest time scale resulting from fitting segmental dynamics correlation functions (gray squares, see also fig. S7).

  • Fig. 5 Segmental motional models derived from C4P reproduce overall NMR relaxation rates better than segmental motional models derived from C3P.

    (A) Top: Length and position of segments derived from C3P (green) and C4P (blue) at 278 K. Bottom: Difference in χ2 of the central residue in the segment between C3P- and C4P-derived segmental models (χ2C3P and χ2C4P). (B and C) Similar representation for segments derived from ensembles of trajectories determined from C3P and C4P at 288 K and 298 K.

  • Fig. 6 Comparison of properties of water models.

    Self-diffusion coefficients (A) and lifetime of hydrogen bonds (B) in TIP3P (blue circles) and TIP4P/2005 (orange squares) water.

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/5/6/eaax2348/DC1

    Table S1. Summary of the MD simulations carried out on the C-terminal domain of Sendai virus and discussed in the present work.

    Table S2. Summary of the results of the ABSURD procedure.

    Fig. S1. Experimental secondary chemical shifts (bars) compared with values calculated using frames extracted from the trajectories every 500 ps as input to SPARTA+.

    Fig. S2. Distribution of radii of gyration in the ensemble used to seed the MD simulations (bars) compared with those calculated using frames extracted from the trajectories every 200 ps.

    Fig. S3. Experimental 15N chemical shift anisotropy/dipole-dipole cross-correlated cross-relaxation rates (ηxy) measured on Ntail compared with the results of simulations.

    Fig. S4. Root-mean-square deviations between experimental and simulated spin relaxation rates at 298K.

    Fig. S5. Root-mean-square deviations between experimental and simulated spin relaxation rates at 288K.

    Fig. S6. Root-mean-square deviations between experimental and simulated spin relaxation rates at 278K.

    Fig. S7. Time scales in the correlation function describing the contribution of backbone dihedral angles dynamics to relaxation of 15N backbone amide nuclei.

    Fig. S8. Time scales in the correlation function describing the contribution of segmental motions to relaxation of 15N backbone amide nuclei.

    Fig. S9. Fluctuations of the relative orientation of peptide planes measured by the order parameter S2seg.

    Fig. S10. Time scales extracted from fits of correlation functions describing the rotational dynamics of segments to mono-exponential decays.

    Fig. S11. Time scales associated with intra-segment dynamics at 288K (orange circles) are compared with the longest time scale resulted from fitting segmental dynamics correlation functions (gray squares).

    Fig. S12. Time scales associated with intra-segment dynamics at 278K (yellow circles) are compared with the longest time scale resulted from fitting segmental dynamics correlation functions (gray squares).

    Reference (61)

  • Supplementary Materials

    This PDF file includes:

    • Table S1. Summary of the MD simulations carried out on the C-terminal domain of Sendai virus and discussed in the present work.
    • Table S2. Summary of the results of the ABSURD procedure.
    • Fig. S1. Experimental secondary chemical shifts (bars) compared with values calculated using frames extracted from the trajectories every 500 ps as input to SPARTA+.
    • Fig. S2. Distribution of radii of gyration in the ensemble used to seed the MD simulations (bars) compared with those calculated using frames extracted from the trajectories every 200 ps.
    • Fig. S3. Experimental 15N chemical shift anisotropy/dipole-dipole cross-correlated cross-relaxation rates (ηxy) measured on Ntail compared with the results of simulations.
    • Fig. S4. Root-mean-square deviations between experimental and simulated spin relaxation rates at 298K.
    • Fig. S5. Root-mean-square deviations between experimental and simulated spin relaxation rates at 288K.
    • Fig. S6. Root-mean-square deviations between experimental and simulated spin relaxation rates at 278K.
    • Fig. S7. Time scales in the correlation function describing the contribution of backbone dihedral angles dynamics to relaxation of 15N backbone amide nuclei.
    • Fig. S8. Time scales in the correlation function describing the contribution of segmental motions to relaxation of 15N backbone amide nuclei.
    • Fig. S9. Fluctuations of the relative orientation of peptide planes measured by the order parameter S2seg.
    • Fig. S10. Time scales extracted from fits of correlation functions describing the rotational dynamics of segments to mono-exponential decays.
    • Fig. S11. Time scales associated with intra-segment dynamics at 288K (orange circles) are compared with the longest time scale resulted from fitting segmental dynamics correlation functions (gray squares).
    • Fig. S12. Time scales associated with intra-segment dynamics at 278K (yellow circles) are compared with the longest time scale resulted from fitting segmental dynamics correlation functions (gray squares).
    • Reference (61)

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