Frontiers in Multiscale Modelling of Photoreceptor Proteins
A. Introduction and Motivation
Photoreceptor proteins are the key molecules for response to and sensing of light in many organisms.1 They mediate a variety of functions in nature such as visual perception, regulation of circadian rhythm, phototaxis and light-oriented growth of plants. Typically, photoreceptor proteins consist of a protein moiety and an embedded chromophore, which is responsible for light absorption at a specific wavelength. Upon illumination, the light absorbed by the chromophore is efficiently converted into molecular energy. This initiates a cascade of biochemical reactions that eventually lead to signal transduction and a physiological response of a cell or of an entire organism. Hence, these proteins represent signal converters that translate light into biological information.2 This energy conversion is increasingly utilized in a wide range of biotechnological applications. For instance: in optogenetics photoreceptors are used to selectively control and monitor neuronal activity.3 This method has already yielded important insights into human problems, including depression, disordered sleep, Parkinson’s disease and schizophrenia. However, in order to exploit the full potential of photoreceptor proteins a detailed molecular level understanding is required. Such a comprehensive understanding can be derived from multiscale simulations.
B. State of the Art
In order to model photoreceptor proteins the combined or hybrid quantum-mechanics/molecular mechanics (QM/MM) scheme is the method of choice.4,5 This multiscale method makes the calculations of large protein-chromophore complexes feasible by treating the chemically active region quantum-mechanically (QM) while describing the protein with efficient force-field-based molecular mechanics (MM). The key steps in setting up the QM/MM simulation involves the partitioning in the QM and MM systems and the choice of suitable methods.
Successful applications of the QM/MM method were recently reported for different families of photoreceptor proteins: retinal proteins,6-9 green fluorescent proteins,10,11 photoactive yellow protein,12,13 phytochromes and flavin binding proteins (cryptochromes14 and BLUF domain15,16).
The idea behind the proposed workshop is bring together leading experts in the field of multiscale simulation of photoreceptor proteins and the corresponding method development. The unifying theme is the derivation of a detailed understanding of the light-induced processes in these proteins. The invited experts work on different photoreceptor protein families but also on different methodologies in this research. Specific questions and challenges are grouped by two main subjects in the photoreceptor protein research:
1) Spectral Tuning describes the effect of the protein environment on the chromophore’s absorption.17-19 The following advances will be discussed:
a. What is the effect of the polarizable force field?
b. What is the optimal strategy to sample the geometries?
c. How to partition the protein in a QM and MM region?
2) Excited state reactivity in photoreceptor proteins will encompass different type of reaction, e.g. photoisomerization, excited state proton transfer.20,21
a. Which approximation can be used for nonadiabatic dynamics?
b. How can intersystem crossings be calculated?
c. What is the role of quantum nuclear effects?
A half-day session will be dedicated for each of the six intriguing questions raised above. Hence, this workshop will bring together scientists who belong to different communities. This unique compilation is expected to facilitate interaction across disciplines and will foster synergetic collaborations that will help to advance the field of photoreceptor proteins.
Maria Andrea Mroginski (Technical University of Berlin) - Organiser
Igor Schapiro (The Hebrew University of Jerusalem) - Organiser
Yael Yogev (Tel Aviv University) - Organiser