**3. CABS Applications to Simulation of Disordered or Unfolded Proteins**

In this section, we review CABS applications to simulations of protein–peptide binding (Section 3.1) and folding of globular proteins (Section 3.2). We briefly discuss modeling results for the binding of three protein–peptide systems and protein folding of one protein system. Figure 4 shows native conformations of these systems determined by X-ray crystallography or NMR. In the figure, they are arranged according to the size of a fully flexible fragment of the modeled system, effective timescales required for a meaningful simulation of their motions, and thus the modeling difficulty: (1) modeling of FxxLF motif peptide docking to an androgen receptor (AR), (2) investigation of binding and folding of an unstructured pKID protein to KIX protein, (3) modeling of p53-derived peptide docking to the MDM2 protein receptor with partially unstructured regions, and (4) simulation of the de novo folding of barnase. The simulations were performed using the CABS-dock method for protein–peptide docking [62] and CABS-flex methodology [72,73] that enable running de novo folding simulations.

**Figure 4.** Presentation of the modeling cases discussed in this work. The modeled systems are arranged according to the size of the fully flexible fragment of the modeled system and the effective timescales required to observe their motions. The regions of the systems that were modeled as fully flexible are marked with red, while the regions in which backbone fluctuations were limited to 1 Å RMSD with beige. The presented millisecond values are approximated up to the order of magnitude.
