(A and B) Model of RRM1 bound to oleic acid (yellow) calculated by Schrödinger GLIDE (Friesner et al., 2004; Friesner et al., 2006). (C) Overlay of the oleic acid bound MD simulation (gray and red) with the apo-state NMR structure (gray and blue) (Ohyama et al., 2011). (D) RNA contact residues (red) in loop 5, helix 2, and strand 4 of the β-sheet are perturbed in oleic acid-bound molecular dynamics simulation (Ohyama et al., 2011). (E and F) A representative snapshot from the MD simulation of MSI1 bound to oleic acid (white) compared to the MSI1-RNA NMR structure (blue) (Ohyama et al., 2011). Panel (E) shows the Gua 1 binding pocket. In the oleic-bound state, the open conformation of loop 5 (L5) orients K88 such that K88 cannot contact Gua 1. W29 is stacked against Q30 and unavailable for stacking against Gua 1. Interaction with the side chain of R61 stabilizes the conformation of W29 in the oleic-bound state. Panel (F) highlights the different conformations of residues that interact with Gua 1, Ura 2, Ade 3, and Gua 4; represented in grey, orange, red, and purple, respectively. (G) Difference of the mean Lipari-Szabo order parameters by residue between the apo and oleic acid-bound states of MSI1. The Lipari-Szabo order parameters for the backbone NH bond vectors, S2, were calculated to quantify the backbone flexibility of the free and oleic acid-bound form of MSI1. The difference of the order parameters, ΔS2 = S2apo−S2MSI−OA, indicates that MSI1-oleic acid complex is more flexible than apo MSI1, with the few exceptions mostly observed at the N-terminus. The secondary structural elements are highlighted at the top. Error bars are calculated from the standard deviation among trajectories.