Advisor

Gwaltney, Steven R.

Committee Member

Mlsna, Debra A.

Committee Member

Emerson, Joseph P.

Date of Degree

12-1-2019

Original embargo terms

Visible to MSU only for 1 Year||forever||12/15/2020

Document Type

Graduate Thesis - Open Access

Major

Chemistry

Degree Name

Master of Science

College

College of Arts and Sciences

Department

Department of Chemistry

Abstract

Interactions between DNA and ligands are important in the rational design of drugs and in research into DNA function. In particular, the interaction of DMZ with DNA structures named “G-quadruplexes” was considered. G-quadruplexes are structures present in telomeres and several oncogenes. The main purpose of this project was to provide a computational tool to study DNA ligand interactions using a variety of molecular modeling techniques that include molecular docking, molecular dynamics simulations (MD) and MM/PBSA (Molecular Mechanics/Poisson Boltzmann Surface Area). We investigated the binding modes and binding affinities of DMZ with c-MYC G-quadruplexes (G4s). We found that the conformation and structural design of the quadruplex can dramatically influence the binding profiles of the ligand. The binding free energies for each site were estimated by the MM/PBSA method. The binding of small molecules to DNA can result in the disruption of oncogene transcription, making it an effective anticancer strategy.

URI

https://hdl.handle.net/11668/16477

Comments

DMZ||G-Quadruplexes||c-MYC

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