Embedding Nonrigid Solutes in an Averaged Environment: A Case Study on Rhodopsins

Abstract

Many simulation methods concerning solvated molecules are based on the assumption that the solvated species and the solvent can be characterized by some representative structures of the solute and some embedding potential corresponding to this structure. While the averaging of the solvent configurations to obtain an embedding potential has been studied in great detail, this hinges on a single solute structure representation. This assumption is re-examined and generalized for conformationally flexible solutes and tested on 4 nonrigid systems. In this generalized approach, the solute is characterized by a set of representative structures and the corresponding embedding potentials. The representative structures are identified by means of subdividing the statistical ensemble, which in this work is generated by a constant-temperature molecular dynamics simulation. The embedding potential defined in the Frozen-Density Embedding Theory is used to characterize the average effect of the solvent in each subensemble. The numerical examples concern the vertical excitation energies of protonated retinal Schiff bases in protein environments. It is comprehensively shown that subensemble averaging leads to huge computational savings compared with explicit averaging of the excitation energies in the whole ensemble while introducing only minor errors in the case of the systems examined.

Subsystem density‐functional theory (update)

“…It was shown that for the solvatochromic shift of the $$$ n\to {\pi}^{\ast } $$$ excitation of acetone in water, the effects of such an approximation are negligible. This observation was confirmed for the vertical excitation energies of protonated retinal Schiff bases in protein environments 169 . Such a strategy was further explored by analyzing the solvent fluctuations and by comparing different methods for the construction of the average solvent density 170 .…”

“…This observation was confirmed for the vertical excitation energies of protonated retinal Schiff bases in protein environments. 169 Such a strategy was further explored by analyzing the solvent fluctuations and by comparing different methods for the construction of the average solvent density. 170 Recently, the effect of averaging over different structures of the solute was also explored within such schemes.…”

“…Such a strategy was further explored by analyzing the solvent fluctuations and by comparing different methods for the construction of the average solvent density 170 . Recently, the effect of averaging over different structures of the solute was also explored within such schemes 171 …”