Figure 5.

Comparison of docking and MSM poses and effect of mutations. (a) Overlay of the pose obtained by high-throughput molecular dynamics (red), the docking prediction (blue) and the residues implicated in binding in the 3PBL coordinates. The new pose obtained by MSM fills the pocket formed by V189^5.39A, and I183^ECL2F and would clash with F197^5.47and F346^6.52 in their crystal structure coordinates. (b) The pose obtained by molecular dynamics provides a rationale for the effect of the two mutations (V189^5.39A, I183^ECL2F). The mutated residues are shown with an asterisk. Rotation of the engineered F183^ECL2 would clash with either the ligand or residue 189, affecting protein stability and ligand affinity. Mutant A189^5.39 would lose favorable packing (van der Waals) interactions by reduction of its sidechain.