Molecular dynamics of structural effects of reactive carbonyl species derivate of lipid peroxidation on bovine serum albumin.

Background: Serum albumin is the most abundant protein in the Mammalia blood plasma at where plays a decisive role in the transport wide variety of hydrophobic ligands. BSA undergoes oxidative modifications like the carbonylation by the reactive carbonyl species (RCSs) 4-hydroxy-2-nonenal (HNE), 4 hydroxy-2-hexenal (HHE), malondialdehyde (MDA) and 4-oxo-2-nonenal (ONE), among others. The structural and functional changes induced by protein carbonylation have been associated with the advancement of neurodegenerative, cardiovascular, metabolic and cancer diseases.

Methods: To elucidate structural effects of protein carbonylation with RCSs on BSA, parameters for six new non-standard amino acids were designated and molecular dynamics simulations of its mono‑carbonylated-BSA systems were conducted in the AMBER force field. Trajectories were evaluated by RMSD, RMSF, PCA, RoG and SASA analysis.

Results: An increase in the conformational instability for all proteins modified with local changes were observed, without significant changes on the BSA global three-dimensional folding. A more relaxed compaction level and major solvent accessible surface area for modified systems was found. Four regions of high molecular fluctuation were identified in all modified systems, being the subdomains IA and IIIB those with the most remarkable local conformational changes. Regarding essential modes of domain movements, it was evidenced that the most representatives were those related to IA subdomain, while IIIB subdomain presented discrete changes.

Conclusions: RCSs induces local structural changes on mono‑carbonylated BSA. Also, this study extends our knowledge on how carbonylation by RCSs induce structural effects on proteins.