Quinone Binding in Bacterial Photosynthetic Reaction Center

Abstract

Quinones play a crucial role in transmembrane electron and proton transfer in proteins, thereby creating a gradient that is utilized for energy conversion. The medicinal properties of these molecules render them important for drug design. The quinone binding site varies considerably across different proteins and any strict binding motif is not defined yet. The bacterial photosynthetic reaction center (BRC) is one such protein with two quinone binding sites - QA and QB. Kinetic studies have shown differently substituted foreign quinones to be good binders at the QA site, however there are no protein structures available with the foreign quinones. The goal of this computational study is to derive a BRC-quinone interaction signature, with different quinones docked at the QA site. The derived signature could pave the way for future computer aided drug design, targeted at quinone binding proteins.Sets of substituted foreign quinones were built and optimized in Gaussian09 and docked into the BRC QA site with AutoDock4.2. The protein-ligand vanderwaals overlap was calculated in Chimera. Analyses of the van der waals interaction of the complexes brought out a pattern of favorable interactions of the ligand with the protein, that directly correlate with high binding affinity. The benzoquinone strong binders showed favorable interaction with TrpM252, MetM256 and MetM262 of the BRC. The methyl and methoxy flanking a carbonyl formed a benzoquinone ligand-motif for strong binding. LeuM215, TrpM252, Met256, PheM258, MetM262, and IleM265 of the receptor favorably interacted with the strong naptho binders. Future work includes Molecular dynamics studies that will involve the FEP method on the docked complexes in NAMD2.9.