Mohammad ASAD, PhD student within the ModES team, will defend his thesis entitled: “Multiscale Modelling Studies of UnaG Fluorescent Protein and its Bilirubin Ligand” on Tuesday November 29 at 2:00 PM in Salle Marie Curie, CEISAM Laboratory.
The present thesis deals with the theoretical investigation of a new class of ligand-induced fluorescent protein, named UnaG. Such protein only emits light in presence of an endogenous ligand, a bilirubin (BLR) and, therefore, has a large panel of applications in medicine to evaluate BLR level, for instance in case of infantile jaundice. Moreover, BLR is also known to be an antioxidant which makes BLR the central work of this PhD thesis. First, molecular dynamics (MD) simulations coupled to hybrid quantum mechanics/molecular mechanics (QM/MM) were carried to evaluate the structural changes of the wild type UnaG behaviors and two known mutants (N57A and N57Q) and to estimate the absorption properties of UnaG and the latter mutants. Such results allow us to get insights on the evolution of their respective quantum yield. Additionally, we have also proposed, designed and evaluated the effect of three in silico single mutations (D81A, I55Y, and R112A) to obtain UnaG mutants which bind at higher affinity with BLR compare to WT UnaG, are more rigid, and enhance the quantum yield. Second, we explore the BLR itself in a polar environment to simulate the absorption properties accounting for the dynamic of the system and we further evaluate the antioxidant activity of BLR using both thermodynamic and kinetic studies of BLR in presence of peroxyl radicals.
UnaG, Bilirubin, fluorescence, Antioxidant, MD, QM/MM, TD-DFT and QM.