Coarse-grained simulations of RNA and DNA duplexes

TL;DR

This paper demonstrates that the HiRe-RNA coarse-grained model combined with REMD can accurately predict RNA and DNA duplex structures and their thermodynamics, enabling efficient simulations of larger nucleic acid molecules.

Contribution

It introduces an application of the HiRe-RNA model to duplexes of RNA and DNA, showing its ability to predict native structures and study dissociation, extending previous work on simple hairpins.

Findings

Successfully predicted RNA duplex structures from random configurations.

Validated the coarse-grained model by comparing atomistic MD dynamics with experimental structures.

Extended the model's application to DNA duplexes, demonstrating versatility.

Abstract

Although RNAs play many cellular functions little is known about the dynamics and thermodynamics of these molecules. In principle, all-atom molecular dynamics simulations can investigate these issues, but with current computer facilities, these simulations have been limited to small RNAs and to short times. HiRe-RNA, a recently proposed high-resolution coarse-grained for RNA that captures many geometric details such as base pairing and stacking, is able to fold RNA molecules to near-native structures in a short computational time. So far it had been applied to simple hairpins, and here we present its application to duplexes of a couple dozen nucleotides and show how with our model and with Replica Exchange Molecular Dynamics (REMD) we can easily predict the correct double helix from a completely random configuration and study the dissociation curve. To show the versatility of our model, we present an application to a double stranded DNA molecule as well. A reconstruction algorithm allows us to obtain full atom structures from the coarse-grained model. Through atomistic Molecular Dynamics (MD) we can compare the dynamics starting from a representative structure of a low temperature replica or from the experimental structure, and show how the two are statistically identical, highlighting the validity of a coarse-grained approach for structured RNAs and DNAs.