Protein and RNA dynamical fingerprinting

• Published in: Nature communications 2019-03, Vol.10 (1), p.1026-1026, Article 1026
• Main Authors: Niessen, Katherine A., Xu, Mengyang, George, Deepu K., Chen, Michael C., Ferré-D’Amaré, Adrian R., Snell, Edward H., Cody, Vivian, Pace, James, Schmidt, Marius, Markelz, Andrea G.
• Format: Article
• Language: English
• Subjects: 631/57; 631/57/2272; 639/624/1107/510; 639/624/1107/527; 639/624/1111/55; Anisotropy; Assessments; BASIC BIOLOGICAL SCIENCES; Biology; biophotonics; biophysics; Birefringence; Data acquisition; Energy Transfer; Fingerprinting; G-Quadruplexes; Humanities and Social Sciences; imaging and sensing; Macromolecular Substances - chemistry; Macromolecules; Microscopy; Models, Theoretical; molecular biophysics; Molecular Dynamics Simulation; multidisciplinary; Nucleotide Mapping - instrumentation; Nucleotide Mapping - methods; optical spectroscopy; Peptide mapping; Peptide Mapping - instrumentation; Peptide Mapping - methods; Protein Conformation; Proteins; Proteins - chemistry; Ribonucleic acid; RNA; RNA - chemistry; Science; Science (multidisciplinary); Sensitivity; Sensitivity analysis; Spectrum Analysis; Steering; Terahertz Imaging - instrumentation; Terahertz Imaging - methods; Vibration; Vibrational spectra; Vibrations; Water - chemistry; Water absorption
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-08926-3

Protein structural vibrations impact biology by steering the structure to functional intermediate states; enhancing tunneling events; and optimizing energy transfer. Strong water absorption and a broad continuous vibrational density of states have prevented optical identification of these vibrations. Recently spectroscopic signatures that change with functional state were measured using anisotropic terahertz microscopy. The technique however has complex sample positioning requirements and long measurement times, limiting access for the biomolecular community. Here we demonstrate that a simplified system increases spectroscopic structure to dynamically fingerprint biomacromolecules with a factor of 6 reduction in data acquisition time. Using this technique, polarization varying anisotropy terahertz microscopy, we show sensitivity to inhibitor binding and unique vibrational spectra for several proteins and an RNA G-quadruplex. The technique’s sensitivity to anisotropic absorbance and birefringence provides rapid assessment of macromolecular dynamics that impact biology. The characterization of biomacromolecule structural vibrations has been impeded by a broad continuous vibrational density of states obscuring molecule specific vibrations. A terahertz microscopy system using polarization control produces signatures to dynamically fingerprint proteins and a RNA G-quadruplex.