Quantum mechanical/molecular mechanical studies of F(1)-ATPase and a plant photoreceptor

Computer simulations of biomolecular systems like enzymes or photoreceptors require the study of a quantum mechanical process inside an extended biomolecular environment. Here, we report quantum mechanical/molecular mechanical (QM/MM) simulations of the chemo-mechanical coupling in F1-ATPase and photoexcitation in a plant blue-light photoreceptor.; The enzyme F1-ATPase is a molecular motor that converts the chemical energy stored in the molecule adenosine tri-phosphate (ATP) into mechanical rotation of its gamma sub-unit. During steady state catalysis, the three catalytic sites of F1 operate in a cooperative fashion such that at every instant each site is in a different conformation corresponding to a different stage along the catalytic cycle. Notwithstanding a large amount of biochemical and, recently, structural data we still lack an understanding of how ATP hydrolysis in F1 is coupled to mechanical motion and how the catalytic sites achieve cooperativity during rotatory catalysis. We have studied ATP hydrolysis in the betaTP betaDP catalytic sites of F1-ATPase. Our simulations reveal a dramatic change in the reaction energetics from strongly endothermic in beta TP to approximately equi-energetic in betaDP. The simulations identify the responsible protein residues, the arginine finger alphaR373 being the most important one. We find a multi-center proton relay mechanism to be the energetically most favorable hydrolysis pathway. The results elucidate how cooperativity between catalytic sites might be achieved by this remarkable molecular motor.; The plant blue-light receptors of the phot family mediate plant phototropism and contain two light, oxygen, and voltage (LOV) sensitive domains as photoactive elements. We have performed QM/MM simulations of the photocycle of a complete Phot-LOV1 domain from C. reinhardtii. We have investigated the electronic properties and structural changes that follow blue-light absorption. This permitted us to characterize the pathway for flavin-cysteinyl adduct formation, which was found to proceed via a neutral radical state generated by hydrogen atom transfer from the reactive cysteine residue, C57, to the chromophore flavin mononucleotide. Interestingly, we find that adduct formation does not cause any larger scale conformational changes in Phot-LOV1 which suggests that dynamical effects mediate signal transmission following the initial photoexcitation event.