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

Area of Science:

• Computational chemistry
• Theoretical chemistry
• Molecular dynamics simulations

Background:

• Current simulation methods for solvated molecules often assume a single representative solute structure.
• Averaging solvent configurations to obtain embedding potentials is well-studied but limited by this single-structure assumption.

Purpose of the Study:

• To re-examine and generalize the single-structure assumption for conformationally flexible solutes.
• To develop a method using a set of representative solute structures and corresponding embedding potentials.
• To test the generalized approach on nonrigid molecular systems.

Main Methods:

• Generating a statistical ensemble of solute configurations using constant-temperature molecular dynamics.
• Identifying representative solute structures by subdividing the statistical ensemble.
• Utilizing Frozen-Density Embedding Theory to define embedding potentials for each subensemble.
• Calculating vertical excitation energies for protonated retinal Schiff bases in protein environments.

Main Results:

• The generalized approach characterizes flexible solutes using multiple representative structures and their embedding potentials.
• Subensemble averaging significantly reduces computational cost compared to averaging over the entire ensemble.
• The method introduces only minor errors for the examined nonrigid systems.

Conclusions:

• Subensemble averaging provides a computationally efficient and accurate method for simulating flexible solvated molecules.
• This generalized approach overcomes limitations of single-structure assumptions in molecular simulations.
• The findings are particularly relevant for calculating electronic properties like excitation energies in complex environments.