Accurate three states model for amino acids with two chemically coupled titrating sites in explicit solvent atomistic constant pH simulations and pK_a calculations.

Correct protonation of titratable groups in biomolecules is crucial for their accurate description by molecular dynamics simulations. In the context of constant pH simulations, an additional protonation degree of freedom is introduced for each titratable site, allowing the protonation state to change dynamically with changing structure or electrostatics. Here, we extend previous approaches for an accurate description of chemically coupled titrating sites. A second reaction coordinate is used to switch between two tautomeric states of an amino acid with chemically coupled titratable sites, such as aspartate (Asp), glutamate (Glu), and histidine (His). To this aim, we test a scheme involving three protonation states. To facilitate charge neutrality as required for periodic boundary conditions and Particle Mesh Ewald (PME) electrostatics, titration of each respective amino acid is coupled to a “water” molecule that is charged in the opposite direction. Additionally, a force field modification for Amber99sb is introduced and tested for the description of carboxyl group protonation. Our three states model is tested by titration simulations of Asp, Glu, and His, yielding a good agreement, reproducing the correct geometry of the groups in their different protonation forms. We further show that the ion concentration change due to the neutralizing “water” molecules does not significantly affect the protonation free energies of the titratable groups, suggesting that the three states model provides a good description of biomolecular dynamics at constant pH

Hydrogen Bonding Controls Excited-State Decay of the Photoactive Yellow Protein Chromophore

International audienceWe have performed excited-state dynamics simulations of a Photoactive Yellow Protein chromophore analogue in water. The results of the simulations demonstrate that in water the chromophore predominantly undergoes single-bond photoisomerization, rather than double-bond photoisomerization. Despite opposite charge distributions in the chromophore, excited-state decay takes place very efficiently from both single- and double-bond twisted minima in water. Radiationless decay is facilitated by ultrafast solvent reorganization, which stabilizes both minima by specific hydrogen bond interactions. Changing the solvent to the slightly more viscous D(2)O leads to an increase of the excited-state lifetime. Together with previous simulations, the present results provide a complete picture of the effect of the protein on the photoisomerization of the chromophore in PYP: the positive guanidinium group of Arg52 favors double-bond isomerization over single-bond isomerization by lowering the barrier for double-bond isomerization, while the hydrogen bonds with Tyr42 and Glu46 enhance deactivation from the double-bond twisted minimum

Arginine52 controls the photoisomerization process in photoactive yellow protein

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