The contribution of folic acid (FA)-tryptophan interactions to FA-protein association was investigated in the context of using FA as a drug carrier in protein delivery systems. Bovine serum albumin (BSA) and indolicidin were used as model proteins in the study. The FA-BSA complex was characterized by using the Bradford reagent to identify the impact of FA-BSA association on BSA-dye reagent interactions. UV-visible spectroscopic analysis of the FA-BSA mixture showed that the absorbance maximum of BSA-dye reagent occurred at 595 nm, even after the association of FA with BSA. This confirms that protonated amino acid groups of the protein are not involved in FA-BSA association. Moreover, molecular dynamics (MD) simulation confirmed the presence of an associative interaction between aromatic moieties in FA and tryptophan moieties in the indolicidin molecule, which disrupted FA self-assembly. An X-ray diffraction (XRD) study showed that there was limited disruption of FA self-assembly after the addition of BSA or tryptophan. This suggests that FA and BSA are compatible and associate with each other. Graphical Abstract Mechanism of folic acid and protein association.
Keywords: Folate; Indolicidin; Molecular dynamics; Spectroscopy; Tryptophan.