Date of Award

Summer 8-8-2017

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Donald Hamelberg

Second Advisor

Ming Luo

Third Advisor

Ivaylo Ivanov

Abstract

The NF-κB family of transcription factors controls a number of essential cellular functions. Pirin is a non-heme iron (Fe) redox specific co-regulator of NF-κB (p65) and has been shown to modulate the affinity between the homodimeric p65 and the DNA. The allosteric effect of the active Fe(III) form of Pirin on the DNA is not known and has not been investigated. We carry out multiple microsecond-long molecular dynamics simulations of the free DNA, p65-DNA complex, and the Pirin-p65-DNA supramolecular complexes in explicit water. We show that, unlike the Fe(II) form of Pirin, the Fe(III) form in the Pirin-p65-DNA supramolecular complex enhances the interactions and affinity between p65 and the DNA, in agreement with experiments. The results further provide atomistic details of the effect of the Fe(III) form of Pirin on the DNA upon binding to p65 to form the supramolecular complex.

DOI

https://doi.org/10.57709/10527205

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