Interactions between wild type (WT) VP35 protein and the F235H mutant with ubiquitin and compounds.

Interactions between wild type (WT) VP35 protein (in gray) and the F235H mutant with ubiquitin (in green) on the left column, pCEBS (in orange, middle column), and SFC (in cyan, right column), with the dash lines representing pairwise atomic interactions that change by more than 0.1 kcal/mol between WT and F235 as predicted by Surfaces. The colors of individual dash lines, as well as the colors of entire residues, are shown in a scale of blue to white in which blue represents more favorable interactions/residues with stronger net interactions and white represents less significant interactions/residues with net interactions closer to null. Compared to WT, we see that the F235H mutation in VP35 strengthens the interaction with residues PRO19, SER57, ASN60, ILE61, and most of all with GLN62 of Ubiquitin (on the right in the 2 left-most panels). Compared to WT, the F235H mutations do not abolish interactions between this residue (H235) for either of the compounds. In both cases, however, the small molecules are predicted to have weaker interactions with residue H235 compared to F235. The overall predicted DG of binding (in kcal/mol) for each complex is displayed in each panel. The difference between the bottom and top DG values for each interaction gives a predicted DDG of −1.57 kcal/mol for the interaction with Ubiquitin, suggesting a strengthening of this interaction, whereas for pCEBS and SFC we obtain positive DDG values of 0.23 kcal/mol and 0.74 kcal/mol, respectively, suggesting that both molecules have a weaker interaction with VP35 in the F235H mutant.

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