Mechanism of Action of Cyclophilin A Explored by Metadynamics Simulations
Figure 3
Collective variables used in bias exchange metadynamics simulations. The red box encloses the variables used in the PEPT-WAT system, the blue box contains variables used in PEPT-CypA. We define briefly each CV as follows: (A) see Figure 2; (B) Proline nitrogen pyramidalization is defined as the distance between P4N atom and the center of the plane determined by G3C-P4Cα-P4Cδ; (C) P4N interaction with water is defined as P4N coordination with O atoms of all water molecules; (D) P4N intramolecular H-bond was defined as P4N coordination with N(-H) atoms of all H-bonds donor residues of PEPT; (E) P4N@PEPT H-bond with PEPT or CypA was described as the coordination of P4N with N(-H) and O(-H) atoms of all possible H-bond donors of PEPT and CypA; (F) R55 H-bond with PEPT-CypA is illustrated as the coordination between R55@CypA and CypA active site residues; (G) Interaction of L98 and S99 with C-terminal part of the substrate is defined as the coordination between non polar carbons atoms of C-terminal@PEPT and those of L99 S99; (H) Hydrophobic interactions between the N and C terminal of PEPT with the active site were described as the coordination of the non polar carbons of the PEPT N-and C-terminal with non polar carbons of the residues in the active site of CypA; I) Non-polar carbons coordination of G3P4@PEPT with CypA active site residues.