RNA model evaluation based on MD simulation of four tRNA analogs

Abstract

High resolution 3D structures of tRNA molecules are scarce. Therefore, there is a burning need for tools aiming at three-dimensional (3D) RNA structure characterization able to provide accurate information on the tertiary structure of ribonucleic acids. In this study, RNA structure assessment based on primary sequence, molecular dynamics (MD) simulations as well as selected RNA model evaluation methods are used to propose and evaluate four mitochondrial tRNA analogs. The 3D structures of tRNA^Ala, tRNA^Gly, tRNA^His, and tRNA^Phe are generated from primary sequence using mFold and RNAComposer, and subjected to 100 ns explicit solvent MD simulations with AMBER. The global and local root-mean-square deviations (RMSD), interaction network fidelity (INF), deformation index (DI), the contact area difference-score (CAD-score) as well as principal component analysis (PCA) revealed that the largest changes occurring during MD simulation were in the D–T and anticodon loops but each of the studied tRNA analog is affected differently. tRNA^Ala and tRNA^Phe undergo limited structure perturbation, mostly in the D–T loops regions, while tRNA^Gly changes the geometry within the anticodon loop. The tRNA^His analog is the most flexible, changes its structure significantly, including separation of the D and T loops. Furthermore, the anticodon loops are visibly more stable than the D–T region and their structure does not change that significantly, except for tRNA^Gly.