Structural Biology and Molecular Biophysics

Predicting the Sequence-Dependent Backbone Dynamics of Intrinsically Disordered Proteins

Sanbo Qin
Huan-Xiang Zhou author has email address

Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, USA
Department of Physics, University of Illinois at Chicago, Chicago, IL 60607, USA

https://doi.org/10.7554/eLife.88958.1

Open access
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Figures and data

Representative conformations of five IDPs. (A-E) MKK4, α-synuclein, Mev-P_NTD, Sev-NT, and CBP-ID4. Conformations were initially generated using TraDES (http://trades.blueprint.org) (46), selected to have radius of gyration close to predicted by a scaling function R_g = 2.54N^0.522 (Å) (47). Conformations for residues predicted as helical by PsiPred plus filtering were replaced by ideal helix. Finally residues are colored according to a scheme ranging from green for low predicted R₂ to red for high predicted R₂.

Properties of the 45 IDPs in the training set. (A) Histograms of means and standard deviations, calculated for individual proteins. Curves are drawn to guide the eye. Inset: correlation between and . (B) Experimental mean scaled R₂ (msR₂) and SeqDYN q parameters, for the 20 types of amino acids. Note that Pro residues have low msR₂ for the lack of backbone amide proton. Amino acids are in descending order of q.

Properties of the 45 IDPs in the training set. (A) Histograms of means and standard deviations, calculated for individual proteins. Curves are drawn to guide the eye. Inset: correlation between and . (B) Experimental mean scaled R₂ (msR₂) and SeqDYN q parameters, for the 20 types of amino acids. Note that Pro residues have low msR₂ for the lack of backbone amide proton. Amino acids are in descending order of q.

SeqDYN model parameters. (A) Correlation between msR₂ and q. The values are also displayed as bars in Fig. 2B. (B) Correlation of msR₂ and q with amino-acid molecular mass. (C) Correlation of msR₂ and q with bulkiness. (D) The optimal correlation length and deterioration of SeqDYN prediction as the correlation length is moved away from the optimal value.

Quality of SeqDYN predictions. (A) Histogram of RMSE(−1). Letters indicate RMSE(−1) values of the IDPs to be presented in panels (B-F). (B-F) Measured (bars) and predicted (curves) R₂ profiles for MKK4, α-synuclein, Mev-P_NTD, Sev-NT, and CBP-ID4. In (E) and (F), green curves are SeqDYN predictions and red curves are obtained after a helix boost.

Measured (bars) and predicted (curves) R₂ profiles for ChiZ N-terminal region, TIA1 prion-like domain, Pdx1 C-terminal region, synaptobrevin-2, α-endosulfine, YAP, AMOTL1, FtsQ, and CAHS-8. In (C), R₂ does not fall off at the N-terminus because the sequence is preceded by an expression tag MGSSHHHHHHHHHHHHS. In (H) and (I), green curves are SeqDYN predictions and red curves are obtained after a helix boost.

Predicted R₂ profiles (curves) for the lysozyme sequence and a mutant show close agreement with those measured (bars) on the proteins in the unfolded state. (A) Wild type. (B) With Trp62 to Gly mutation.

RMSEs (s⁻¹) of R₂ predictions by SeqDYN and MD for 10 IDPs

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