Computational methods toward accurate RNA structure prediction using coarse-grained and all-atom models.
Computational methods can provide significant insights into RNA structure and dynamics, bridging the gap in our understanding of the relationship between structure and biological function. Simulations enrich and enhance our understanding of data derived on the bench, as well as provide feasible alternatives to costly or technically challenging experiments. Coarse-grained computational models of RNA are especially important in this regard, as they allow analysis of events occurring in timescales relevant to RNA biological function, which are inaccessible through experimental methods alone. We have developed a three-bead coarse-grained model of RNA for discrete molecular dynamics simulations. This model is efficient in de novo prediction of short RNA tertiary structure, starting from RNA primary sequences of less than 50 nucleotides. To complement this model, we have incorporated additional base-pairing constraints and have developed a bias potential reliant on data obtained from hydroxyl probing experiments that guide RNA folding to its correct state. By introducing experimentally derived constraints to our computer simulations, we are able to make reliable predictions of RNA tertiary structures up to a few hundred nucleotides. Our refined model exemplifies a valuable benefit achieved through integration of computation and experimental methods.
Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
Andrey
A
Krokhotin
Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA. Electronic address: dokh@unc.edu.
Nikolay V
NV
Dokholyan
D020029:Base Pairing; D019277:Entropy; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D010710:Phosphates / Q000737:chemistry; D012313:RNA / Q000737:chemistry*; D059370:RNA Folding; D012984:Software
D010710:Phosphates; D012313:RNA
All-atom model; Coarse-grained model; DMD; Prediction; RNA; Structure