Fig. 3: Free energy landscape for the WPD-loop closed-to-open conformational change in PTP1B.
From: Activation and friction in enzymatic loop opening and closing dynamics
a Free energy profile for the closed (left) to open (right) transition along the s path-CV. The shaded region corresponds to the statistical uncertainty; b Average RMSD measured for the backbone atoms of the WPD-loop for snapshots obtained from the Umbrella Sampling simulations along the path-CV with respect to the X-ray structures (PDB 6B90) corresponding to the closed (blue) and open (red) states. The shaded region corresponds to the statistical uncertainty (95% confidence interval); c Projection of the MFEP along the antisymmetric combinations of the two distances and two dihedral angles used as CVs. The yellow dot indicates the position of the Transition State; d Evolution of the individual CVs (distances on the right vertical axis and dihedrals on the left vertical axis) along the MFEP. The CVs used in the ASM calculations are: ψ181, ϕ182 torsional angles and the distances Asp181Cγ-Arg221Cζ (d1) and Asp181Cγ-Arg112Cζ (d2). Vertical lines indicate the stages of the process discussed in the text.
