Data-Driven Discovery of the Origins of UV Absorption in the Alpha-3C Protein

Over the past decade, there has been a growing body of experimental work showing that proteins devoid of aromatic and conjugated groups can absorb light in the near-UV beyond 300 nm and emit visible light. Understanding the origins of this phenomenon offers the possibility of designing noninvasive spectroscopic probes for local interactions in biological systems. It was recently found that the synthetic protein α₃C displays UV-vis absorption between 250 and 800 nm, which was shown to arise from charge-transfer excitations between charged amino acids. In this work, we use data-driven approach to re-examine the origins of these features using a combination of molecular dynamics and excited-state simulations. Specifically, an unsupervised learning approach beginning with encoding protein environments with local atomic descriptors is employed to automatically detect relevant structural motifs. We identify three main motifs corresponding to different hydrogen-bonding patterns that are subsequently used to perform QM/MM simulations, including the entire protein and solvent bath with the density-functional tight-binding (DFTB) approach. Hydrogen-bonding structures involving arginine and carboxylate groups appear to be the most prone to near-UV absorption. We show that the magnitude of the UV-vis absorption predicted from the simulations is rather sensitive to the size of the QM region employed as well as to the inclusion of explicit solvation.