File S1 - Discrete Molecular Dynamics Can Predict Helical Prestructured Motifs in Disordered Proteins

Figure S1–S3 and Table S1. Figure S1. α-helical propensities in KID using RX-DMD. RX-DMD simulations using 8 replicas were performed for all the experimentally investigated proteins with PresMo, collected in the review of Lee et al. [1] α-helical propensities of the conformational ensembles at each simulation temperature were determined and plotted as described in Methods. KID is shown as an example, while the results for all other proteins and temperatures can be found at http://disorder.hegelab.org. Green boxes: PresMo regions determined experimentally [2], [3]. Figure S2. Comparing RX-DMD and Agadir predictions. Helical contents of the 24 protein segments with experimentally determined PreSMos were also predicted using Agadir [4]. From 65 PreSMos in these proteins 18 were detected by Agadir at 5% threshold based on the work of Bystroff and Garde [5], while 45 were detected by RX-DMD. Interestingly, in many cases when Agadir and RX-DMD match exactly the same regions, such as in the case of the first PreSMo in KID presented in this figure. In addition, RX-DMD finds 32 PreSMos not detected experimentally, while Agadir does 8. It is important to note that these numbers do not necessary indicate false positives, since many PreSMos might exist and be not visible by NMR because of their rate of conformational transitions. Agadir and RX-DMD predictions are identical in many cases also in the case of PresMos not detected by experiments that may be employed to filter out false positives. Black: RX-DMD; blue: Agadir. Figure S3. Rg distribution of α-Synuclein ensembles from RX-DMD simulations is similar to that determined in experiments [6]. Table S1. Prediction of RX-DMD compared to complexes observed in X-ray structures. Four segments from transmembrane proteins and 86 segments out of 97 PDB entries, which exhibited at least one region with 20% of helical propensity, are listed. From this 90 segments in 36 cases were the prediction in good agreement with the experimental results (only a few a.a. difference). This observation suggests that significant portion of PresMos have a direct role in binding and are MoREs. *sequences and their boundaries can be found at http://disorder.hegelab.org. **marks selected membrane proteins.
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