Interaction of Mg(II), Ca(II), Sr(II), and Ba(II) vitamin B2 complexes with riboflavin kinase: a theoretical study.

Riboflavin (RF), or vitamin B2, is an important redox cofactor whose biological function can be modulated by metal coordination. In the current study, experimental investigation and Density Functional Theory (DFT), molecular docking, and molecular dynamics (MD) simulations were conducted on RF and its alkaline-earth metal complexes, such as Mg(II), Ca(II), Sr(II), and Ba(II): [M(RF)2(X)2]; X = Cl or NO3, to illustrate their structural and electronic behavior toward riboflavin kinase (RFK). DFT calculations at the B3LYP/LanL2DZ level confirmed bidentate coordination via carbonyl oxygen and azomethine nitrogen atoms, leading to electronically stable geometries with enhanced charge delocalization. Docking studies showed that metal coordination strengthens the binding affinity, while the Mg(II) complex demonstrated the most favorable interaction energy at -10.8 kcal mol− 1. On the other hand, MD simulations presented that the RFK-[Mg(RF)2(Cl)2] complex possesses greater structural stability, tighter folding, and stronger hydrogen-bonding interactions than free riboflavin. Overall, the Mg(II) coordination significantly enhanced electronic stability and binding efficiency in riboflavin, showing molecular insights into the understanding of the modulation of vitamins by metals and designing improved bioactive cofactors.