Role of Bulk Water Environment in Regulation of Functional Hydrogen-Bond Network in Photoactive Yellow Protein.

Photoactive yellow protein is a soluble photoreceptor protein involved in signal transduction for phototaxis. A hydrogen-bond between the chromophore, p-coumaric acid (pCA), and a nearby carboxyl group of Glu46 at the active site is known to play a crucial role in the formation of the signaling state in the photoactivation. Since the hydrogen-bond at the active site as well as the extensive conformational changes of the protein in the formation of the signaling state are considered to be controlled by water molecules, we theoretically examined influence of bulk water environment on the functionally important hydrogen-bond by means of molecular simulations. Theoretical analysis of potential energy profiles of the proton transfer between pCA and Glu46 with quantum mechanical/molecular mechanical (QM/MM) calculations revealed critical effect of electrostatic screening of bulk water on the electronic character of the hydrogen-bond. Moreover, QM/MM free energy geometry optimizations identified the water-penetrating state where Glu46 forming a putative low-barrier hydrogen-bond with pCA is hydrated by water molecules penetrating from bulk environment in addition to the water-excluded state which corresponds to X-ray crystallographic structures. The present results suggest that the water-penetrating state is a precursory conformational substate that leads to efficient formation of the signaling state.