The aim of the workshop is to bring together leading experts in the field of theoretical and experimental investigation of photoreceptor proteins, excited state properties of biological matter, and charge transfer processes, providing a state-of-the-art picture of our current knowledge and future challenges of this cutting edge interdisciplinary topic. 

Ground-breaking recent results that contribute to the achievement of a deeper understanding of the mechanisms of photoresponsive biomolecules at the microscopic level will be presented, as well as methodological
challenges and advances to reach a robust and reliable description of the involved complex processes.

Specific open issues will encompass:

• Interplay between the photoexcitation and the environment conformational rearrangements. Hybrid quantum/classical approaches are typical methods to account for both the configurational complexity of the environment (e.g., protein matrix). Recent advances improved the interaction between the quantum and classical regions by including mutual polarization.
• Treatment of reaction events occurring out of equilibrium. The photoexcitation induces significant changes in both the electronic and nuclear structure of the chromophore and its surroundings. Photoresponsive biological systems will encompass different types of reactions, which include
  photoisomerization, excited state proton transfer, etc. We will discuss which approximations can be used for nonadiabatic dynamics and how intersystem crossings can be described.
• Investigation of the reaction path at the molecular level. The understanding of the molecular mechanisms affecting the excited state lifetime and the photoexcitation quantum yield is of broad interest for practical applications. However, the origin of the different behaviors observed in different systems is
  still unclear.
• Cutting-edge applications in relevant fields. Recent results on the modeling of complex biomolecular systems that find application in the fields of optogenetics, enzymatic photocatalysis, photosynthesis and DNA photodamage will provide an overview of the knowledge in these relevant and timely fields.
• Latest advances in the experimental probing of photoresponsive biomolecules. The experimental
  investigation of photoactive molecules poses significant challenges such as the achievement of a controlled photostimulation in native conditions and real-time probing of events spanning a wide time range (from hundreds of femtoseconds to several nanoseconds).

Background

Nature uses light to control biological systems by means of photoresponsive molecules. Such molecules are found, for example, as chromophores in proteins or nucleic acids. The spatio-temporal precision of the interaction between light and these molecules offers many exciting possibilities for applications in highly relevant fields such as those of optogenetics, enzymatic photocatalysis, artificial photosynthesis and the investigation of DNA photodamages. All these applications hold the promise for major advances across a broad spectrum of scientific and technological domains.

Optogenetics, for instance, exploiting the genetic encoding of photoactive proteins to control physiological processes, has revolutionized neurosciences, answering many relevant questions about what causes neuropsychiatric disorders [1].  This technology also gave relevant contributions to other fields (e.g, the investigation of cardiac tissue, stem cells, and biosignaling). One highlight is a clinical study demonstrating partial recovery of vision in a human subject using channelrhodopsin [2]. In the emerging field of enzymatic photocatalysis, combination of the high specificity and efficiency of enzymes with the benefits of photocatalysis opens the way to a more sustainable chemical synthesis [3]. Similarly, the final goal of artificial photosynthesis is to use sunlight to drive chemical reactions and produce clean energy [3,4]. Understanding light induced structural alterations in DNA is essential for both preventing and developing treatments for UV-related cancers [5].

Despite their break-through potential, the above-mentioned applications of photoresponsive biomolecules are still far from being fully realized and key limitations still exist. The current inability to overcome some of these limitations mainly arises from the lack of understanding of the relationship between the structural/dynamical properties of these proteins and their photochemistry. This knowledge is however a prerequisite for e.g. engineering the next generation of optogenetics tools or to unlock new catalytic functions in natural and artificial enzymes [6,7]. Theoretical/computational approaches have been essential in providing a deeper comprehension of photoresponsive biomolecules at the molecular level, complementing experimental spectroscopies, protein engineering and structure-guided mutagenesis [8-10]. The functioning mechanism is affected by several interconnected processes that follow photoexcitation, such as electronic excitation of the chromophore and subsequent charge distribution alteration, protein conformational changes, and different relaxation pathways. Remarkably, charge transfer processes (i.e. electron, proton and proton coupled electron transfer reactions) have been identified as key events.

The proper treatment of these complex processes using computational methods has several challenges. The combined quantum mechanics/molecular mechanics (QM/MM) approaches are particularly suitable to investigate the relevant systems and physicochemical phenomena: the light-induced reaction is extremely fast (from hundreds of fs to tens of ps) and its mechanism is highly influenced by the spatial constraints of the protein matrix. Yet, suitable electronic structure models to treat both ground and excited states have to be employed, as well as their degeneracy at conical intersections [11]. More robust and automated protocols for QM/MM simulations are also desired [12]. Another key point is the inclusion of mutual polarization effects between the chromophore and the surrounding protein environment [13]. The fact that the protein-chromophore interactions are not limited to electrostatic effects should also be considered [14]. These are some of the current challenges that will be addressed during the workshop. The relevance of these theoretical/computational issues for technological applications will be reappraised in thorough discussions also involving leading experimental scientists in the field.