A Set of Quantum-Mechanically Derived Force Fields for Natural and Synthetic Retinal Photoswitches

Abstract

The diverse biological functions of rhodopsins are all triggered by the photoexcitation of retinal protonated Schiff base chromophores. This diversity can be traced back not only to variations in protein scaffolds in which the chromophore is embedded, but also to the different isomeric forms of the chromophore itself, whose role is crucial in several processes. Although most computational approaches for these systems often require classical molecular dynamics, efforts in providing a set of parameters able to accurately and consistently model several isomeric chromophores are lacking in the literature. The most recent efforts entail either refinements of general purpose force fields lacking in accuracy, or parametrization strategies that include environmental effects, which makes the resulting parameters not transferable to a different embedding. In this work, we provide accurate intramolecular force fields based on data purposely computed using Møller–Plesset second order perturbation theory, specifically tailored for varied natural retinal protonated Schiff bases and synthetic analogues often employed in retinal-based photoswitches. We demonstrate the quality of our quantum-mechanically derived force fields (QMD-FFs) through a wide set of validation tests. These consistently indicate that QMD-FFs outperform in all cases transferable, general-purpose FFs, delivering an excellent description of each chromophore in terms of equilibrium geometries, conformational landscapes, and optical properties in comparison to literature data, experimental measurements, and reference QM calculations. Our intramolecular QMD-FFs, distributed in electronic format, can be adopted to describe these chromophores in complex environments, exploiting intermolecular parameters compatible with those available in the literature for biological macromolecules.