Molecular dynamics simulation of cytochrome b5: implications for protein-protein recognition.

Cytochrome b5 participates in electron-transfer reactions with a variety of different proteins. To explore how this protein might discern between structurally varied proteins, we have performed a molecular dynamics simulation focusing on its structural stability and dynamic behavior in solution. The protein was simulated in water at 298 K and pH 6.9 for 2.5 ns. The protein deviated significantly from the crystal structure midway through the simulation, but ultimately the crystalline conformation was regained. The simulation was at all times well behaved as judged by comparison to structural NMR data obtained in solution. One region of the protein backbone that deviated from the crystal conformation contains acidic residues implicated in electrostatic-based protein-protein recognition. The mobility in this region caused the protein to display different patterns of residues at the surface with time, as well as the formation of a large cleft partially exposing the hydrophobic core lining the heme pocket. Furthermore, the position and cyclical formation of this cleft suggest that hydrophobic interactions may be important in protein-protein recognition events and possibly even electron transfer, as the cleft allows for easy access to the heme group. These results indicate that thermal motion could provide a low-energy mechanism for controlling recognition events. Thus, the dynamical behavior observed through the varying solution conformations sampled may be important in influencing the diverse range of protein-protein interactions in which cytochrome b5 participates.