The use of interatomic contact areas to quantify discrepancies between RNA 3D models and reference structures

Abstract

Growing interest in computational prediction of ribonucleic acid (RNA) three-dimensional structure has highlighted the need for reliable and meaningful methods to compare models and experimental structures. We present a structure superposition-free method to quantify both the local and global accuracy of RNA structural models with respect to the reference structure. The method, initially developed for proteins and here extended to RNA, closely reflects physical interactions, has a simple definition, a fixed range of values and no arbitrary parameters. It is based on the correspondence of respective contact areas between nucleotides or their components (base or backbone). The better is the agreement between respective contact areas in a model and the reference structure, the more accurate the model is considered to be. Since RNA bases account for the largest contact areas, we further distinguish stacking and non-stacking contacts. We have extensively tested the contact area-based evaluation method and found it effective in both revealing local discrepancies and ranking models by their overall quality. Compared to other reference-based RNA model evaluation methods, the new method shows a stronger emphasis on stereochemical quality of models. In addition, it takes into account model completeness, enabling a meaningful evaluation of full models and those missing some residues.