MD simulations of Nucleic Acids

Multiple biological processes involve the stretching of nucleic acids (NA). Stretching forces induce local changes in the molecule structure, inhibiting or promoting the binding of proteins, which ultimately affects their functionality. Understanding how a force induces changes in the structure of nucleic acids at the atomic level is a challenge. To investigate local NA structural changes induced by mechanical stress one may resort to all atom molecular dynamics (MD) simulations. MD can access the atomic detail of a NA structure  and provide information about the mechanical response of the chain as a whole.

We are interested in studying the mechanical properties of nucleic acids using all-atom MD simulations and the role their structure may play in functional DNA-protein interactions.

In a recent work, we have used microsecond-long molecular dynamics to simulate the structure of dsDNA and dsRNA subjected to stretching forces up to 20 pN. We determine all the elastic constants of dsDNA and dsRNA and provide an explanation for three striking differences in the mechanical response of these two molecules: the three-fold softer stretching constant obtained for dsRNA, the opposite twist-stretch coupling and its non-trivial force dependence. The lower dsRNA stretching resistance is linked with its more open structure, while the opposite twist-stretch coupling of both molecules is due to the very different evolution of molecule’ inter-strand distance with the stretching force. A reduction of this distance leads to overwinding in dsDNA. In contrast, dsRNA is not able to reduce its inter-strand distance and can only elongate by unwinding. Inter-strand distance is directly correlated with the slide base pair parameter and its different behaviour in dsDNA and dsRNA traced down to changes in the sugar pucker angle of these nucleic acids.

Want to learn more? See the topic-related papers of the group

Marín-González*, Vilhena*, Moreno-Herrero and Perez. bioRxiv  doi: DNA crookedness regulates DNA mechanical properties at short length scales.

Marín-González*, Vilhena*, Perez and Moreno-Herrero. Proceedings of the National Academy of Sciences USA 114(27), 7049-7054 (2017). doi: 10.1073/pnas.1705642114. Double stranded DNA and RNA under constant stretching forces: atomistic insights from microsecond-long molecular dynamics. LINK


Universidad Autonoma de Madrid: Ruben Perez’s Group