Unknotting RNA : A method to resolve computational artifacts

Abstract

RNA 3D structure prediction often encounters entanglements, computational artifacts that complicate structural models, resulting in their exclusion from further studies despite the potentially accurate prediction of regions outside the entanglement. This study presents a protocol aimed at resolving such issues in RNA models while preserving the overall 3D fold and structural integrity. By employing the SPQR coarse-grained model and short Molecular Dynamics simulations, the protocol imposes energy terms that enable selective modifications to disentangle structures without causing significant distortions. The method was validated on 195 entangled RNA models from CASP15 and RNA-Puzzles, successfully resolving over 70% of interlaces and approximately 40% of lassos, with minimal impact on the original geometry but notable improvement in ClashScore. The efficiency of untangling conformations that are unequivocally classified as artifacts is 81%. Certain cases, particularly those involving dense packing of atoms or complex secondary structures, posed challenges that limited the efficiency of the method. In this paper, we present quantitative results from the application of the protocol and discuss examples of both successfully disentangled and unresolved structures. We show a viable approach for refining models previously deemed unsuitable due to topological artifacts.