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.
Bibliographical noteFunding Information:
The authors thank the cofunding project of the University of Geneva and the Hebrew University of Jerusalem Israel for financing this collaboration. Igor Schapiro acknowledges the German Research Foundation via the SFB-1078 project C6. Igor Schapiro is thankful for the support by the Israel Science Foundation (Research Center grant no. 3131/20). Jonathan R. Church thanks the Zuckerman STEM Leadership Program for their support. Suliman Adam acknowledges the Minerva Stiftung for a postdoctoral fellowship within the framework of the Minerva Fellowship Program.
© 2023 The Authors. Published by American Chemical Society.