Figure 4.

Molecular dynamics simulation of cis/trans isomerization by TF^PPD. A, plots of the ω dihedral angle for the peptidyl–prolyl bond between MBP Gly²⁵⁴ and Pro²⁵⁵. The simulation was started from the NMR structure of MBP–TF^PPD complex in which the ω angle for the peptidyl–prolyl bond between MBP Gly²⁵⁴ and Pro²⁵⁵ is −174° (trans state). Because of the ω angle constraint at a rate of 0.2° per 2 ps, the ω angle changed linearly as a function of time. B, plots of the distance between the H^N atom of TF Ile¹⁹⁵ and the carbonyl oxygen of MBP Gly²⁵⁴ as a function of time when the ω angle was rotated clockwise (blue) or counterclockwise (red). When the ω angle was rotated in clockwise direction, the two atoms approached each other, and the distance became shorter than 2.5 Å at ∼0.8 ns. As seen in A, the ω dihedral angle at 0.8 ns was at approximately −90° (syn state). C and D, snap shots of the cis/trans isomerization at the trans state (0.200 ns) (C) and the syn state (0.794 ns) (D). The intermolecular hydrogen bond between backbone amide group of TF^PPD Ile¹⁹⁵ and the backbone carbonyl oxygen of MBP Gly²⁵⁴ is formed at the syn state, which tethers the peptidyl–prolyl bond closer onto the hydrophobic cleft formed by TF^PPD Ile¹⁹⁵, Phe²¹⁷, and Pro²¹⁸.