P-FARFAR2: A multithreaded greedy approach to sampling low-energy RNA structures in Rosetta FARFAR2

Abstract

RNA (ribonucleic acid) structure prediction finds many applications in health science and drug discovery due to its importance in several life regulatory processes. But despite significant advances in the close field of protein prediction, RNA 3D structure still poses a tremendous challenge to predict, especially for large sequences. In this regard, the approach unfolded by Rosetta FARFAR2 (Fragment Assembly of RNA with Full-Atom Refinement, version 2) has shown promising results, but the algorithm is non-deterministic by nature. In this paper, we develop P-FARFAR2: a parallel enhancement of FARFAR2 that increases its ability to assemble low-energy structures via multithreaded exploration of random configurations in a greedy manner. This strategy, appearing in the literature under the term “parallel mechanism”, is made viable through two measures: first, the synchronization window is coarsened to several Monte Carlo cycles; second, all but one of the threads are differentiated as auxiliary and set to perform a weakened version of the problem. Following empirical analysis on a diverse range of RNA structures, we report achieving statistical significance in lowering the energy levels of ensuing samples. And consequently, despite the moderate-to-weak correlation between energy levels and prediction accuracy, this achievement happens to propagate to accuracy measurements.