The measured and calculated affinity of methyl- and methoxy-substituted benzoquinones for the Q(A) site of bacterial reaction centers.

Quinones play important roles in mitochondrial and photosynthetic energy conversion acting as intramembrane, mobile electron, and proton carriers between catalytic sites in various electron transfer proteins. They display different affinity, selectivity, functionality, and exchange dynamics in different binding sites. The computational analysis of quinone binding sheds light on the requirements for quinone affinity and specificity. The affinities of 10 oxidized, neutral benzoquinones were measured for the high affinity Q(A) site in the detergent-solubilized Rhodobacter sphaeroides bacterial photosynthetic reaction center. Multiconformation Continuum Electrostatics was then used to calculate their relative binding free energies by grand canonical Monte Carlo sampling with a rigid protein backbone, flexible ligand, and side chain positions and protonation states. Van der Waals and torsion energies, Poisson-Boltzmann continuum electrostatics, and accessible surface area-dependent ligand-solvent interactions are considered. An initial, single cycle of GROMACS backbone optimization improves the match with experiment as do coupled-ligand and side-chain motions. The calculations match experiment with an root mean square deviation (RMSD) of 2.29 and a slope of 1.28. The affinities are dominated by favorable protein-ligand van der Waals rather than electrostatic interactions. Each quinone appears in a closely clustered set of positions. Methyl and methoxy groups move into the same positions as found for the native quinone. Difficulties putting methyls into methoxy sites are observed. Calculations using a solvent-accessible surface area-dependent implicit van der Waals interaction smoothed out small clashes, providing a better match to experiment with a RMSD of 0.77 and a slope of 0.97. Copyright 2010 Wiley-Liss, Inc.