Coarse-Grained Models of RNA Nanotubes for Large Time Scale Studies in Biomedical Applications.

Shyam Badu,Sanjay Prabhakar,Roderick Melnik

doi:10.3390/biomedicines8070195

Shyam Badu, Sanjay Prabhakar + Show 1 more

Open Access

https://doi.org/10.3390/biomedicines8070195

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Abstract

In order to describe the physical properties of large time scale biological systems, coarse-grained models play an increasingly important role. In this paper we develop Coarse-Grained (CG) models for RNA nanotubes and then, by using Molecular Dynamics (MD) simulation, we study their physical properties. Our exemplifications include RNA nanotubes of 40 nm long, equivalent to 10 RNA nanorings connected in series. The developed methodology is based on a coarse-grained representation of RNA nanotubes, where each coarse bead represents a group of atoms. By decreasing computation cost, this allows us to make computations feasible for realistic structures of interest. In particular, for the developed coarse-grained models with three bead approximations, we calculate the histograms for the bond angles and the dihedral angles. From the dihedral angle histograms, we analyze the characteristics of the links used to build the nanotubes. Furthermore, we also calculate the bead distances along the chains of RNA strands in the nanoclusters. The variations in these features with the size of the nanotube are discussed in detail. Finally, we present the results on the calculation of the root mean square deviations for a developed RNA nanotube to demonstrate the equilibration of the systems for drug delivery and other biomedical applications such as medical imaging and tissue engineering.

Highlights

The accurate modeling of the complex biomolecules like ribonucleic acid (RNA) nanoclusters is important for many biological processes taking place in the human body, as well as for their applications such as drug delivery
By using coarse-grained molecular dynamics simulations of RNA nanotubes, which have not been reported anywhere, we systematically study the mechanical properties of RNA
Using molecular dynamics simulations we modeled a range of different RNA nanotubes of various sizes

Summary

Introduction

The accurate modeling of the complex biomolecules like ribonucleic acid (RNA) nanoclusters is important for many biological processes taking place in the human body, as well as for their applications such as drug delivery. Molecular Dynamics (MD) simulation on complex biological systems, such as RNA nanotubes, for sufficiently large time scales of interest. The development and detailed analysis of all-atom molecular dynamics simulations and coarse-grained models of RNA nanotubes become imperative [8,24,25,27,28,29,30,31,32,33,34,35]. By using MD simulations based on coarse-grained models, we study the structural and physical properties of such nanoscale biological systems, which provided such characteristics as radial distributions and histograms for the bond and dihedral angles. Prior studies were performed on such structures as 16-RNA molecules and 10-RNA protein complexes and some others by using generic sets of coarse-grained model parameters, with details given in [40,41,42], but not on RNA nanotubes

Background of CG Model

Computational Details

Results and Discussion

Conclusions

Methods