Combining Experimental Restraints and RNA 3D Structure Prediction in RNA Nanotechnology

Abstract

Precise RNA tertiary structure prediction can aid in the design of RNA nanoparticles. However, most existing RNA tertiary structure prediction methods are limited to small RNAs with relatively simple secondary structures. Large RNA molecules usually have complex secondary structures, including multibranched loops and pseudoknots, allowing for highly flexible RNA geometries and multiple stable states. Various experiments and bioinformatics analyses can often provide information about the distance between atoms (or residues) in RNA, which can be used to guide the prediction of RNA tertiary structure. In this chapter, we will introduce a platform, iFoldNMR, that can incorporate non-exchangeable imino protons resonance data from NMR as restraints for RNA 3D structure prediction. We also introduce an algorithm, DVASS, which optimizes distance restraints for better RNA 3D structure prediction.

Keywords: DMD; Discrete molecular dynamics; Distance geometry; NMR; RNA 3D structure prediction; RNA nanoparticle; RNA nanotechnology; RNA restraints; iFoldRNA.