Unravelling Electronic Structure and Molecular Vibrations of Proteins in Virus Using Novel Correlated Plasmon‐Enhanced Raman Spectroscopy With Machine Learning

Abstract Proteins are believed to contain vital functional information of biosystems. In virus, structural proteins form the building blocks of the virus particle. Raman spectroscopy is a powerful technique to probe electronic structure at molecular vibration levels. However, due to weak Raman cross‐section, there is no reliable conventional Raman spectroscopy on E‐proteins in the virus. Herewith, a novel, non‐destructive and direct technique, named correlated plasmon‐enhanced Raman spectroscopy (CP‐ERS) is developed to directly probe electronic and molecular vibrations of proteins. Intriguingly, using CP‐ERS, new resonant quasielastic and inelastic electronic Raman scatterings and phonon excitations of E‐proteins in dengue virus (DENV) are discovered. The CP‐ERS is utilizing newly‐developed highly oriented gold‐quantum dots chips exhibiting low‐loss tunable correlated‐plasmons, high structural stability and reproducibility. By modifying E‐protein, anomalous glycosylation‐induced changes in CP‐ERS are observed. Moreover, CP‐ERS are used for training a machine learning algorithm, obtaining 100% accuracy in hold‐out and 93% mean accuracy in grouped 5‐fold cross‐validation. Our result reveals new resonant quasielastic and inelastic Raman scatterings and new phonons of E‐proteins in viruses and demonstrates a strategy in utilizing CP‐ERS with machine learning to directly measure and quantify electronic structure and structural and molecular vibrations of biological and solid state systems.