Sutthibutpong, T. | bioRxiv Science

bioRxiv2025

Nucleosome-mediated conformational switches in micro-eccDNAs

Extrachromosomal-circular DNA (eccDNA) are circular-DNA elements that are implicated in cellular processes such as genomic diversification and instability, along with other genomic mechanisms. However, their structure and chromatinization state is poorly understood. Here we identified a 358-bp circular micro-eccDNA molecule derived from the human Titin gene, which was selected for this study based on its size and sequence characteristics, and used atomistic molecular dynamics simulations to study its interaction with nucleosomes and corresponding topological state. We show the presence or absence of bound nucleosomes provides a topological switch between intact and denatured DNA.

biophysics↗

bioRxiv2021

Molecular Dynamics Study on the Effects of Charged Amino Acid Distribution Under low pH Condition to the Unfolding of Hen Egg White Lysozyme and Formation of Beta Strands.

Aggregation of unfolded or misfolded proteins into amyloid fibrils can cause various diseases in humans. However, the fibrils synthesized in vitro can be developed toward useful biomaterials under some physicochemical conditions. In this study, atomistic molecular dynamics simulations were performed to address the mechanism of beta-sheet formation of the unfolded hen egg white lysozyme (HEWL) under a high temperature and low pH. Simulations of the protonated HEWL at pH 2 and the non-protonated HEWL at pH 7 were performed at the highly elevated temperature of 450 K to accelerate the unfolding, followed by the 333 K temperature in some previous in vitro studies. The simulations showed that HEWL unfolded faster and refolded into structures with higher beta-strand contents at pH 2. The mechanism of beta-strand formation at the earlier stage of amyloidosis was addressed in terms of the radial distribution of amino acids, affected by the high protonation level at a low pH.

biophysics↗