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Excited State Reaction Path Computations in Proteins

Final Activity Report Summary - EXCPROT (Excited state reaction path computations in proteins)

The present project has been concerned with computational chemistry studies of a certain family of proteins whose action are initiated by the absorption of light by a molecule (a so-called chromophore) bound to the protein. Specifically, the project has investigated the photochemical reactivity of rhodopsin proteins, which are associated with a variety of biological functions and are found in many different organisms. The use of theoretical methods in place of traditional experimental techniques represents an alternative approach to the study of these systems, with many distinct advantages. For example, using theoretical methods, it is possible to extract information that otherwise is difficult, time-consuming, costly, or even impossible to obtain. While computer hardware and software - the computational chemist's basic tools - are under constant development, it is nevertheless clear that performing accurate theoretical studies of systems as large as proteins still constitutes a formidable challenge. This holds true especially for proteins involved in photochemical processes, which occur in electronically excited states and inevitably require a more elaborate methodological framework than ground-state processes. In the present project, novel computational chemistry methods have been employed that face this challenge by integrating an advanced quantum mechanical description of the light-absorbing chromophore, with a description of the surrounding protein based on less elaborate classical force field methods.

The project has primarily been concerned with the photochemical reactivity of a newly discovered member of the rhodopsin family - Anabaena sensory rhodopsin (ASR). This protein occurs in a freshwater cyanobacterium, and is believed to function as a photoreceptor adjusting the composition of the photosynthetic reaction centra in response to the colour of available light. Like all other rhodopsins, ASR harbors a retinal chromophore, which upon light absorption triggers the photochemical activity of the protein by rotating around one of its chemical bonds in a so-called isomerisation reaction. On the other hand, ASR is a unique member of the rhodopsin family in that it exhibits photochromicity. This means that the protein exists in two stable forms, both of which are functionally active, and that these can be reversibly converted into one another by exposure to light of the appropriate wavelength. By studying the detailed mechanism underlying the photochromicity, we have demonstrated that the interconversion process is driven by retinal continuously isomerising in the same direction. Remarkably, this means that ASR can be viewed as a biological realisation of a molecular rotor. To the best of our knowledge, this is the first time that such a feature has been attributed to a photoreceptor protein.

Furthermore, we have identified exactly how this phenomenon comes into force in this particular protein. Besides a wealth of biological implications, these findings offer an interesting perspective for current research in nanotechnology aimed at constructing molecular machines externally fuelled by light and heat only. Throughout the project, a concerted effort has been made to ensure that the accuracy of the underlying calculations is such that experimental data, whenever available, are adequately reproduced, so as to allow for well-founded conclusions.