MD simulation analysis of the Q144R and wild type CYP1B1 structure.

Panel A shows the distribution of the first three major principal components of the Q144R and wild type (WT) structures. The distributions are observed to be different, suggesting an altered functional motion in the Q144R mutant. Panel B shows the altered flexibility pattern of the Q144R mutant as compared to WT. The log2 ratio is calculated as . Therefore a positive value indicates an increase in flexibility in the Q144R mutant and a negative value indicates a decrease in flexibility as compared to WT CYP1B1. The Q144R mutant has a significantly altered flexibility pattern within the C-D, F and G'-H block region, shown separately in the right hand side of the panel. Panel C shows the altered tunnels in two different orientations (top and bottom view) of the Q144R and WT CYP1B1 structures. The upper panel of "Tunnel properties" shows the radius (in bar plot) and length (in black line) of the tunnels (top view orientation) in the mutant (blue) and WT (green) structures. The lower panel shows the similar properties of the tunnels observed in the bottom view orientation. Panel D shows docked retinol in the WT and mutant CYP1B1 structures. The panel also shows an overall decrease in binding energy in retinol binding for the mutant protein, observed through MD simulation.