alpha-Synuclein conformations followed by vibrational optical activity. Simulation and understanding of the spectra

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F21%3A73607479" target="_blank" >RIV/61989592:15310/21:73607479 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.rsc.org/en/content/articlelanding/2021/CP/D1CP02574K" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2021/CP/D1CP02574K</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d1cp02574k" target="_blank" >10.1039/d1cp02574k</a>

Jazyk výsledku

angličtina

Název v původním jazyce

alpha-Synuclein conformations followed by vibrational optical activity. Simulation and understanding of the spectra

Popis výsledku v původním jazyce

alpha-Synuclein is a neuronal protein which adopts multiple conformations. These can be conveniently studied by the spectroscopy of vibrational optical activity (VOA). However, the interpretation of VOA spectra based on quantum-chemical simulations is difficult. To overcome the hampering of the computations by the protein size, we used the Cartesian tensor transfer technique to investigate links between the spectral shapes and protein structure. Vibrational circular dichroism (VCD) and Raman optical activity (ROA) spectra of alpha-synuclein in disordered, alpha-helical and beta-sheet (fibril) forms were measured and analyzed on the basis of molecular dynamics and density functional theory computations. For the disordered and alpha-helical conformers, a high fidelity of the simulated spectra with a reasonable computational cost was achieved. Most experimental spectral features could be assigned to the structure. So far unreported ROA marker bands of the secondary structure were found for the lower-frequency and CH stretching vibrations. Fibril VCD spectra were simulated with a rigid periodic model of the geometry and the results are consistent with previous studies based on cryogenic electron microscopy. The fibrils also give a specific ROA signal, but unlike VCD it is currently not fully explicable by the simulations. In connection with the computational modeling the VOA spectroscopy thus appears as an extremely useful tool for monitoring alpha-synuclein and other proteins in solutions.

Název v anglickém jazyce

alpha-Synuclein conformations followed by vibrational optical activity. Simulation and understanding of the spectra

Popis výsledku anglicky

alpha-Synuclein is a neuronal protein which adopts multiple conformations. These can be conveniently studied by the spectroscopy of vibrational optical activity (VOA). However, the interpretation of VOA spectra based on quantum-chemical simulations is difficult. To overcome the hampering of the computations by the protein size, we used the Cartesian tensor transfer technique to investigate links between the spectral shapes and protein structure. Vibrational circular dichroism (VCD) and Raman optical activity (ROA) spectra of alpha-synuclein in disordered, alpha-helical and beta-sheet (fibril) forms were measured and analyzed on the basis of molecular dynamics and density functional theory computations. For the disordered and alpha-helical conformers, a high fidelity of the simulated spectra with a reasonable computational cost was achieved. Most experimental spectral features could be assigned to the structure. So far unreported ROA marker bands of the secondary structure were found for the lower-frequency and CH stretching vibrations. Fibril VCD spectra were simulated with a rigid periodic model of the geometry and the results are consistent with previous studies based on cryogenic electron microscopy. The fibrils also give a specific ROA signal, but unlike VCD it is currently not fully explicable by the simulations. In connection with the computational modeling the VOA spectroscopy thus appears as an extremely useful tool for monitoring alpha-synuclein and other proteins in solutions.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Physical Chemistry Chemical Physics

ISSN

1463-9076

e-ISSN

—

Svazek periodika

23

Číslo periodika v rámci svazku

31

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

16635-16645

Kód UT WoS článku

000678727500001

EID výsledku v databázi Scopus

2-s2.0-85112716259