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An investigation of folic acid–protein association sites and the effect of this association on folic acid self-assembly

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Abstract

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.

Mechanism of folic acid and protein association

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Abbreviations

Arg:

Arginine

BSA:

Bovine serum albumin

FA:

Folic acid

Ile:

Isoleucine

Leu:

Leucine

Lys:

Lysine

MD:

Molecular dynamics

Pro:

Proline

RDF:

Radial distribution function

Trp:

Tryptophan

XRD:

X-ray diffraction

θ :

Angle

Å:

Angstrom

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Acknowledgements

We acknowledge the Department of Science and Technology, New Delhi, India for providing financial support under project RP02519. Support from the Council of Scientific and Industrial Research (CSIR) New Delhi, India for providing senior research fellowship (SRF) is highly appreciated.

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Authors and Affiliations

  1. Department of Chemical Engineering, Indian Institute of Technology Delhi, New Delhi, India, 110016

    Rajat Gupta, Prasanta Kalita, Omkar Patil & Sanat Mohanty

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  1. Rajat Gupta
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  2. Prasanta Kalita
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Correspondence to Sanat Mohanty.

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Gupta, R., Kalita, P., Patil, O. et al. An investigation of folic acid–protein association sites and the effect of this association on folic acid self-assembly. J Mol Model 21, 308 (2015). https://doi.org/10.1007/s00894-015-2847-2

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