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An enumerative stepwise ansatz enables atomic-accuracy RNA loop modeling.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 12/20/2011, Vol. 108 Issue 51, p20573-20578. 6p. - Publication Year :
- 2011
-
Abstract
- Atomic-accuracy structure prediction of macromolecules should be achievable by optimizing a physically realistic energy function but is presently precluded by incomplete sampling of a biopolymer's many degrees of freedom. We present herein a working hypothesis, called the "stepwise ansatz," for recursively constructing well-packed atomic-detail models in small steps, enumerating several million conformations for each monomer, and covering all build-up paths. By making use of high-performance computing and the Rosetta framework, we provide first tests of this hypothesis on a benchmark of 15 RNA loop-modeling problems drawn from riboswitches, ribozymes, and the ribosome, including 10 cases that are not solvable by current knowledge-based modeling approaches. For each loop problem, this deterministic stepwise assembly method either reaches atomic accuracy or exposes flaws in Rosetta's all-atom energy function, indicating the resolution of the conformational sampling bottleneck. As a further rigorous test, we have carried out a blind all-atom prediction for a noncanonical RNA motif, the C7.2 tetraloop/receptor, and validated this model through nucleotide-resolution chemical mapping experiments. Stepwise assembly is an enumerative, ab initio build-up method that systematically outperforms existing Monte Carlo and knowledge-based methods for 3D structure prediction. [ABSTRACT FROM AUTHOR]
- Subjects :
- *RNA
*MACROMOLECULES
*BIOPOLYMERS
*MONOMERS
*MONTE Carlo method
*RIBOSWITCHES
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 108
- Issue :
- 51
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 70120722
- Full Text :
- https://doi.org/10.1073/pnas.1106516108