Figure 7.

The eNOE is sensitive to minor populated states in the Pin1 WW domain. (a) Free-energy landscapes and cluster populations from replica-exchange molecular dynamics (MD) simulations and maximum entropy-based chemical shift reweighing carried out at 303 K are shown. The upward facing red triangles indicate cluster centroids that have a higher population in the reweighed ensemble (RE) than the canonical ensemble. The downward pointing triangles indicate clusters that have a lower population. For more information, see reference [35]; (b) Root-mean-square deviation (RMSD) violations of cross-relaxation rate constants from bidirectional (top) and unidirectional (bottom) eNOEs from REs and canonical ensembles (CEs), as well as from the native and near-native conformational clusters at 303 K. RMSD violations of 0.1–0.2 s^—1 translate into distance errors of approximately 0.3–0.4 Å. Secondary structure by residue (black lines indicate loops and coiled regions, and blue blocks indicate β strands) are shown on x-axis; (c) The conformational changes inherent to the native and near-native states are depicted by calculated structural ensembles. The change in loop 1 (residues 17–20, top) of the WW domain and the topological rearrangement of the N and C termini (bottom) are especially prevalent. Ten conformers are shown in each cluster. This figure was adapted from [35], Copyright (2016), with permission from Cell Press.