Fig. 2.

Cryptic site assessment. (A), CryptoSite indices mapped onto the TRMT2A RRM (shown in cartoon representation). Values ranging from gray, unlikely part of a cryptic site to red, higher probability of contributing to a cryptic site. On the helical site of the RRM, W134 and L135 were detected as putative contributors to cryptic site formation. (B), Rear view of the RRM with the identified subpockets and consistent numbering in b, c, and d with TRAPP. All appearing transient regions are depicted as isosurfaces (at 25% occurrence during the simulation). Binding site residues are depicted as sticks. (C), Representative TRAPP binding site flexibility estimation (RMSD values in Å are color-coded from white to red) using the L-RIP/RIPlig approaches. W134, H83, and K135 show high structural variance. (D), Subpocket occurrence during the simulations shows that all four subpockets are formed repeatedly. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)