Sufficient minimal model for DNA denaturation: Integration of harmonic scalar elasticity and bond energies

Abstract

We study DNA denaturation by integrating elasticity — as described by the Gaussian network model — with bond binding energies, distinguishing between different base pairs and stacking energies. We use exact calculation, within the model, of the Helmholtz free-energy of any partial denaturation state, which implies that the entropy of all formed “bubbles” (“loops”) is accounted for. Considering base pair bond removal single events, the bond designated for opening is chosen by minimizing the free-energy difference for the process, over all remaining base pair bonds. Despite of its great simplicity, for several known DNA sequences our results are in accord with available theoretical and experimental studies. Moreover, we report free-energy profiles along the denaturation pathway, which allow to detect stable or meta-stable partial denaturation states, composed of bubble, as local free-energy minima separated by barriers. Our approach allows to study very long DNA strands with commonly available computational power, as we demonstrate for a few random sequences in the range 200-800 base-pairs. For the latter, we also elucidate the self-averaging property of the system. Implications for the well known breathing dynamics of DNA are elucidated.

The 1-Particle-per-k-Nucleotides (1PkN) Elastic Network Model of DNA Dynamics with Sequence-Dependent Geometry

“…Recently proposed CG models can accurately reproduce some of the properties observed in experiments (Freeman et al, 2014a; Hinckley and de Pablo, 2015; Markegard et al, 2015; Snodin et al, 2015; Singh and Granek, 2016) or all-atom models (Savelyev and Papoian, 2010; Setny and Zacharias, 2013; Naômé et al, 2014), which also depend on solution conditions. However, due to the large degrees of freedom, the computational cost of these models is still not low enough to be applicable to long DNA sequences containing more than 10 4 base pairs, corresponding to a 10-nm fiber with 100 nucleosomes or a mitochondrial nucleoid.…”