Figure 4.

Computational Modeling and Biochemical Investigation of ERK2-Lig-D Interactions

(A) Overlay of the final trajectories of 100 ns molecular dynamics simulations of the ERK2-Lig-D binding interaction with ERK2 in the oxidized (ERK2 in cyan; Lig-D in royal blue) and reduced (ERK2 in green; Lig-D in white) states.

(B) Close-up of the region boxed in A. Key residues in ERK2 and Lig-D are labeled in the color corresponding to the respective model. An H-bond that forms between Lig-D^N15 and the backbone carbonyl of ERK2^T158 in the oxidized state is shown (solid orange line). Likewise, the distance between the sulfenylated form of C159 (CSO159) and ERK2^H123 in the oxidized state is shown (dashed yellow line).

(C) Coulombic surface representation of ERK2-Lig-D showing the positions of Lig-D^L14 and Lig-D^L16 relative to hydrophobic pockets A and B (φ_A and φ_B, respectively) in the DRS.

(D) Relative activity of ERK2 toward Sub-D (blue) or Sub-D(N15D) following oxidation of ERK2 with the indicated concentrations of H₂O₂. Data points and error bars are as in Figure 2E. Statistically significant differences between ERK2 activity toward Sub-D and Sub-D(N15D) are indicated by an asterisk (∗, p < 0.05). All structure images were generated using UCSF Chimera software (https://www.cgl.ucsf.edu/chimera/).