Applying machine learning to understand photoprotection: how do triazine-based UV-filters really work?

Summary:
Ultraviolet radiation (UVR) has far-reaching consequences on life such as skin cancer in humans and damage to photosynthetic machinery in plants. This project will study the fundamental mechanisms that provide naturally-occurring molecules with photoprotective properties, allowing them to absorb UVR and dissipate it harmlessly as heat. We will harness the power of Machine-Learned Potential Energy Surfaces to accelerate electronic structure calculations based on Time- Dependent Density Functional Theory, which are accurate but far too slow for dynamics. This will enable calculations of properties such as excited state lifetimes in a complex solvent environment. One main target of this will be triazine-based UV filters found in commercial sunscreen formulations.

Background:
Ultraviolet radiation (UVR) within the solar spectrum has far-reaching consequences on human, animal and plant life: it is of course a well-known cause of skin cancers, and while sunlight is necessary for photosynthesis in plants, UVR also damages photosynthetic machinery and increases susceptibility to invading pathogens. The proposed research focuses on studying the fundamental mechanisms that provide naturally-occurring molecules with photoprotective properties.

Enabling such simulations requires dramatic acceleration of ab initio dynamics, which is possible through the use of Machine-Learned Potential Energy Surfaces based on neural networks trained on DFT data. The ESTEEM code under development at Warwick is a Python package for machine learning of potential energy surfaces of excited states of molecules in solvents: we can learn to perform dynamics with ab initio accuracy fast enough to generate hundreds or thousands of trajectories that are long - at least on quantum mechanical timescales (100s of picoseconds).

We will use these dynamics models to study UVR interaction with triazine-based UV filters found in commercial sunscreen formulations by electronic structure-based dynamical simulations complementing time-resolved spectroscopy experiments. This combination holds the key to establishing a rigorous structure-dynamics-function picture of the energy dissipation mechanisms operating in these molecules (for example intramolecular proton transfer between phenolic OH and triazine N in Tinosorb S) as well as their fidelity for ground state recovery so that they are available for numerous absorption/recovery cycles.

Such studies will allow us to quantify the effects of: solvent; pH; modification of molecular structure; and blend (mixture with emollient) on the UV filters. This will also enable us to garner an unprecedented understanding of the photochemistry of these UVFs, in as-close to real-use conditions as possible. Importantly, such a 'structure-dynamics-function' approach may enable us to establish 'innovative design rules' for next generation UVFs which tackle industrial challenges in formulation science such as: (1) increased sun protection factor (SPF), (2) increased critical wavelength (> 370 nm), and (3) increased photostability of up to 90% after 2 hours of exposure.

Impact on Students. The primary impact will be on the 50+ PhD students trained by the Centre. They will be high-quality computational scientists who can develop and implement new methods for modelling complex systems in collaboration with scientists and end-users, who are comfortable working in interdisciplinary environments, have excellent communication skills and be well prepared for a wide range of future careers. The students will tackle and disseminate results from exciting PhD projects with strong potential for direct impact. Exemplar research themes we have identified together with our industrial and international partners: (i) design of electronic devices, (ii) catalysis across scales, (iii) high-performance alloys, (iv) direct drive laser fusion, (v) future medicine exploration, (vi) smart nanofluidic interfaces, (vii) composite materials with enhanced functionality, (viii) heterogeneity of underground systems.

Impact on Industry. Students trained by HetSys will make a significant impact on UK industry as they will be ideally prepared for R&D careers to help to address the skills shortage in science and engineering. They will be in high demand for their ability to (i) work across disciplines, (ii) perform calculations that come along with error estimates, and (iii) develop well-designed software that other researchers can readily use and modify which implements novel solutions to scientific problems. More generally, incorporating error bars into models to take account of incomplete data and insufficient models could lead to significantly enhanced adoption of materials modelling in industry, reducing trial and error, and costly/time-consuming R&D procedures. The global market for simulation software is expected to more than double from now to 2022 indicating a very strong absorptive capacity for graduates. Moreover, a recent European Materials Modelling Consortium report identified a typical eight-fold return on investment for materials modelling research, leading to cost savings of 12M Euros per industrial project.

Impact on Society. Scarcity of resources and high energy requirements of traditional materials processing techniques raise ever-increasing sustainability concerns. Limitations on jet engine fuel efficiency and the difficulties of designing materials for fusion power stations reflect the social and economic cost of our incomplete knowledge of how complex heterogeneous systems behave. High costs of laboratory investigations mean that theory must aid experiment to produce new knowledge and guidance. By training students who can develop the new methodology needed to model such issues, HetSys will support society's long term need for improved materials and processes.

There will also be a direct impact locally and regionally through engagement by HetSys in outreach projects. For example we will encourage CDT students to be involved with annual 'Inspire' residential courses at Warwick for Year 11 girls, which will show what STEM subjects are like at degree level. CDT students will present highlights from projects to secondary-school pupils during these courses and also visit local schools, particularly in areas currently under-represented in the student body, in coordination with relevant professional bodies.

Impact on collaboration. Our international partners have identified the same urgent challenges for computational modelling. We will build flourishing links with research institutes abroad with long term benefit on UK research via our links to computational science networks. Shared research projects will strengthen links between academic staff and industry R&D personnel and across disciplines. The work will also lead to accessible, robust and reusable software. The Centre will achieve cross-disciplinary academic impact on the physical and materials sciences, engineering, manufacturing and mathematics communities at Warwick and beyond, and on the generation of new ideas, insights and techniques.