Extending the multiscale simulation toolbox for a comprehensive understanding of photoreceptor proteins

The scope of this joint proposal is the application of multiscale modeling for the systematic study of photoreceptor proteins and their mutants. Photoreceptor proteins are the key molecules for response to and sensing of light in many organisms. They mediate a variety of functions in nature such as visual perception, regulation of circadian rhythm, phototaxis and light-oriented growth of plants. However, due to the large size of these proteins their computational studies are challenging. The unfavorable scaling of quantum chemical methods renders any explicit treatment of the environment unfeasible. Multi-scale methods -i.e. based on interfacing treatment at different levels of theory for different parts of the system- were hence developed as solutions to this problem. Frozen Density Embedding Theory (FDET) [1,2] uses the electron density of the environment (ρB) to describe its effect on a system of interest. While maintaining a quantum-level description of the whole system, FDET allows for the use of any method for generating ρB, including experimental densities and time-averaged densities from Molecular Dynamics (MD) simulations.[3]  Furthermore, FDET could be interfaced with quantum mechanics/molecular mechanics (QM/MM) resulting in a QMA/QMemb/MM approach for an even better trade-off between accuracy and computational cost.     MD simulations provide a comprehensive insight into the time evolution of light induced processes.[4,5,6] Such reactions often have non-adiabatic effects that enable efficient transfer of electronic excitation energy to nuclear kinetic energy and vice versa, often causing irreversible transfer of potential energy to heat, or form a unique mechanism for reactions which are forbidden in the adiabatic framework. With our collaboration we aim to explore the possibilities of combining FDET with nonadiabatic molecular dynamics and QM/MM simulations to study photoreceptor proteins. Participants