Bulletin of ANPA

Abstract submitted to ANPA Conference July 14–16, 2023

Volume 5, Number 1

Biological, Medical, Soft Matter and Chemical Physics

Abstract ID: ANPA2023-N00032

Abstract:

ANPA2023-N00032: Mechanistic insights into nucleic acid interaction of hTOP3B using molecular dynamics simulations

Authors:

• Yasir Mamun; Department of Chemistry and Biochemistry, Florida International University

• Yuk-Ching Tse-Dinh; Department of Chemistry and Biochemistry, Florida International University

• Prem Chapagain; Department of Physics, Florida International University

• ; Biomolecular Sciences Institute, Florida International University

Human topoisomerase III beta (hTOP3B) is the only type IA topoisomerase in humans that works on both DNA and RNA substrates. This enzyme plays a crucial role in neurological development in mammals. Recently it has been found that hTOP3B is important for positive-sense single-stranded RNA viruses to replicate efficiently, making it a potential antiviral drug target. Although type IA topoisomerases of different organisms have been studied over the years, the step-by-step interaction of hTOP3B and nucleic acid substrates is still not elucidated. Molecular dynamics (MD) simulation is a tool for studying protein-substrate interaction, and we utilized this method to study the interactions between hTOP3B and nucleic acids. For this, we generated multiple models of hTOP3B complexed with DNA and RNA sequences using the hTOP3B crystal structure (PDB: 5GVC) and 8-mer single-stranded DNA and RNA sequences. These modeled complexes include both covalently and non-covalently complexed structures. We then performed MD simulations of all the modeled complexes. From the simulations, we can highlight the stability of the complexes, conformational changes, sequence preference, and interactions of the binding pocket residues with different nucleotides. Our work demonstrates that hTOP3B forms stable complexes with both RNA and DNA and highlights the suitability of the complexes for inhibitor discovery and binding study. It also provides a better understanding of the enzyme’s interaction with different nucleic acid substrate sequences.

To cite this abstract, use the following reference: https://anpaglobal.org/conference/2023/ANPA2023-N00032