Integrated Computational Study of the Light-Activated Structure of the AppA BLUF Domain and Its Spectral Signatures.
Shaima HashemGiovanni Battista AlteriLorenzo CupelliniBenedetta MennucciPublished in: The journal of physical chemistry. A (2023)
We apply an integrated approach combining microsecond MD simulations and (polarizable) QM/MM calculations of NMR, FTIR, and UV-vis spectra to validate the structure of the light-activated form of the AppA photoreceptor, an example of blue light using flavin (BLUF) protein domain. The latter photoactivate through a proton-coupled electron transfer (PCET) that results in a tautomerization of a conserved glutamine residue in the active site, but this mechanism has never been spectroscopically proven for AppA, which has been always considered as an exception. Our simulations instead confirm that the spectral features observed upon AppA photoactivation are indeed directly connected to the tautomer form of glutamine as predicted by the PCET mechanism. In addition, we observe small but significant changes in the AppA structure, which are transmitted from the flavin binding pocket to the surface of the protein.
Keyphrases
- molecular dynamics
- electron transfer
- molecular dynamics simulations
- density functional theory
- optical coherence tomography
- monte carlo
- amino acid
- binding protein
- magnetic resonance
- protein protein
- high resolution
- transcription factor
- gene expression
- magnetic resonance imaging
- genome wide
- mass spectrometry
- computed tomography