Non-B DNA conformations analysis through molecular dynamics simulations

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Pina, AF (Author) Other; Sergio Filipe Sousa (Author) FCUP; Azevedo, L (Author) Other; Carneiro, J (Author) Other

Journal

Title: Biochimica et Biophysica Acta - General Subjects

Vol. 1866

ISSN: 0304-4165

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-00X-AWM

DOI: 10.1016/j.bbagen.2022.130252

Abstract (EN): Background: Non-B DNA conformations are molecular structures that do not follow the canonical DNA double helix. Mutagenetic instability in nuclear and mitochondrial DNA (mtDNA) genomes has been associated with simple non-B DNA conformations, as hairpins or more complex structures, as G-quadruplexes. One of these structures is Structure A, a cloverleaf-like non-B conformation predicted for a 93-nt (nucleotide) stretch of the mtDNA control region 5 '-peripheral domain. Structure A is embedded in a hot spot for the 3 ' end of human mtDNA deletions revealing its importance in influencing the mutational instability of the mtDNA genome.Methods: To better characterize Structure A, we predicted its 3D conformation using state-of-art methods and algorithms. The methodologic workflow consisted in the prediction of non-B conformations using molecular dynamics simulations. The conservation scores of alignments of the Structure A region in humans, primates, and mammals, was also calculated.Results: Our results show that these computational methods are able to measure the stability of non-B confor-mations by using the level of base pairing during molecular dynamics. Structure A showed high stability and low flexibility correlated with high conservation scores in mammalian, more specifically in primate lineages.Conclusions: We showed that 3D non-B conformations can be predicted and characterized by our methodology. This allowed the in-depth analysis of the structure A, and the main results showed the structure remains stable during the simulations.General significance: The fine-scale atomic molecular determination of this type of non-B conformation opens the way to perform computational molecular studies that can show their involvement in mtDNA cellular mechanisms.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11