期刊
RNA
卷 15, 期 2, 页码 189-199出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1261/rna.1270809
关键词
RNA structure; 3D RNA structure prediction; knowledge-based energy function; coarse-grained modeling
资金
- NIH Roadmap for Medical Research Grant [U54 GM072970]
- NIH [P01-GM66275]
- NSF [0443508]
- RNA Ontology Consortium
- National Library of dicine Training Grant [LM-07033]
- NIH Biotechnology Training Grant [5 T32GM008412-15]
- Damon Runyon Cancer Foundation Research Fellow
- NIGMS [K99-GM079953]
Understanding the function of complex RNA molecules depends critically on understanding their structure. However, creating three-dimensional (3D) structural models of RNA remains a significant challenge. We present a protocol (the nucleic acid simulation tool [NAST]) for RNA modeling that uses an RNA-specific knowledge-based potential in a coarse-grained molecular dynamics engine to generate plausible 3D structures. We demonstrate NAST's capabilities by using only secondary structure and tertiary contact predictions to generate, cluster, and rank structures. Representative structures in the best ranking clusters averaged 8.0 +/- 0.3 A and 16.3 +/- 1.0 angstrom RMSD for the yeast phenylalanine tRNA and the P4-P6 domain of the Tetrahymena thermophila group I intron, respectively. The coarse-grained resolution allows us to model large molecules such as the 158-residue P4-P6 or the 388-residue T. thermophila group I intron. One advantage of NAST is the ability to rank clusters of structurally similar decoys based on their compatibility with experimental data. We successfully used ideal small-angle X-ray scattering data and both ideal and experimental solvent accessibility data to select the best cluster of structures for both tRNA and P4-P6. Finally, we used NAST to build in missing loops in the crystal structures of the Azoarcus and Twort ribozymes, and to incorporate crystallographic data into the Michel-Westhof model of the T. thermophila group I intron, creating an integrated model of the entire molecule. Our software package is freely available at https://simtk.org/home/nast.
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