Dynamics of the firefly luciferase-oxyluciferin complex in its electronic ground and excited states are studied using various theoretical approaches. By mimicking the physiological conditions with realistic models of the chromophore oxyluciferin, the enzyme luciferase, and solvating water molecules and by performing real time simulations with a molecular dynamics technique on the model surfaces, we reveal that the local chromophore-surrounding interaction patterns differ rather severely in the two states. Because of the presence of protein, the solvation dynamics of water around the chromophore is also peculiar and shows widely different time scales on the two terminal oxygen atoms. In addition, simulations of the emission with the quantum-mechanics/molecular-mechanics approach show a close relationship between the emission color variation and the environmental dynamics, mostly through electrostatic effects from the chromophore-surrounding interaction. We also discuss the importance of considering the time scales of the luminescence and the dynamics of the interaction.

Interpolated potential energy surfaces (PESs) have been used for performing reliable molecular dynamics (MD) simulations of small molecular reactions. In this article, we extend this method to MD simulations in condensed phase and show that the same scheme can also be feasibly used when it is supplemented with additional terms for describing intermolecular interactions. We then apply the approach for studying the resolvation process of coumarin 153 in a number of polar solvents. We find that the interpolated surface actually reproduces experimentally found features much better than the conventional force field based potential especially in terms of both dynamics Stokes shift in the short time limit and solute vibrational decoherence. This shows that the solute vibrational effect is important to some degree along the resolvation and should be modeled properly for accurate description of the related dynamics. The stability issue of trajectories on the interpolated PESs is also discussed, in regard to the goal of reliably performing long time simulations. Operational limitations of the present scheme are also discussed.

Construction of force field parameters of the oxyluciferin molecule on its electronic ground and excited states is presented. Several new approaches are introduced for more reliable parameterization: argon-scanning, Hessian matching, and constrained-group parameterization. The Ar-scanning approach is for fitting Lennard-Jones parameters so that the constructed force field can mimic the changes in ab initio energy of oxyluciferin-argon pair at various argon positions. The Hessian matching procedure is to closely reproduce the second derivative matrix of the bonded interaction terms of the force field functions, in comparison with the quantum chemically obtained results. The constrained-group algorithm is applied for both of these approaches to enable an automated atom-type-based parameterization. For complete description of the force field of the oxyluciferin molecule, we have also adopted the second order perturbatively corrected one-particle density matrices to obtain the atomic partial charges within the conventional framework of the restrained electrostatic potential fit. With the availability of the full force field parameter sets, the differences in condensed-phase dynamics on the two states can be investigated. As a simple demonstration, molecular dynamics simulations of aqueous oxyluciferin solution have been performed. The surrounding water structures for the two cases are analyzed by inspecting both the static solvent distribution functions as well as time variation of solvent-solute interaction. The contributions of charge-charge and dispersive interactions toward the solvation dynamics are also discussed.