Modeling the Unbinding Mechanism of the Neutral and Anionic Semi-Quinone from the QA Site of Bacterial Reaction Centers Using Steered Molecular Dynamics Simulations

Abstract

Bacterial photosynthetic reactions centers are large integral membrane proteins that carry out a series of light initiated electron transfer reactions between bound co-factors. In the QA binding site ubiquinone is singly reduced to the anionic semi-quinone. Previous experimental studies using hydroxyl quinones at a pH above the pKa, showed that neutral and anionic quinone species have similar affinity for the QA site (Madeo et. al Biochemistry, 2005, 44 10994-11004). Despite this, anionic quinones dissociate from the QA site 10⊥3 times more slowly than neutral quinones. This suggests that there are large kinetic barriers created by the protein for the dissociation of anionic quinones that are not present in the neutral state. The present study further investigates these barriers by applying constant-velocity steered molecular dynamics (SMD) to compare the unbinding of the neutral native ubiquinone and its anionic semiquinone. The same starting structure (1aij.pdb) is used in ubiquinone and semiquinone simulations, with partial charges adjusted to represent the equilibrated residue charge states. All simulations were performed with the GROMACS package with the OPLS-AA force field. A structural analysis of the trajectories generated during the unbinding of quinones identifies residues of the protein making stronger interactions with semiquinone than with ubiquinone and thus possibly contributing to the kinetic barriers. The magnitude of the energetic barrier is compared to the measured dissociation rate of anionic hydroxyl quinones. Supported by NSF-MCB-1022208.