Representative conformations of five IDPs. (A-E) MKK4, α-synuclein, Mev-PNTD, Sev-NT, and CBP-ID4. Conformations were initially generated using TraDES (http://trades.blueprint.org) (49), selected to have radius of gyration close to predicted by a scaling function Rg = 2.54N0.522 (Å) (50). Conformations for residues predicted as helical by PsiPred plus filtering were replaced by an 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 R̄2 and σR2. (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-PNTD, 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) R2profiles 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), R2does 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.

R2 profiles predicted (curves) by SeqDYN show close agreement with those measured (bars) on structured proteins in the unfolded state. (A) Wild-type lysozyme (8 M urea; pH 2; cysteine-methylated). (B) Lysozyme with Trp62 to Gly mutation (pH 2). Methylated cysteines were treated as Ala in the SeqDYN predictions. (C) Apomyoglogin (8 M urea; pH 2.3). (D) Ubiquitin (8 M urea; pH 2).

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

Dynamics is a crucial link between sequence and function for intrinsically disordered proteins (IDPs). Qin and Zhou developed a sequence-based method to predict IDP dynamics. The predictions provide deep physicochemical insight and can also serve as indicators of properties including phase-separation propensities of IDP sequences.