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J Chem Theory Comput. 2017 Feb 14;13(2):900-915. doi: 10.1021/acs.jctc.6b00870. Epub 2017 Jan 24.

Revised RNA Dihedral Parameters for the Amber Force Field Improve RNA Molecular Dynamics.

Author information

1
Department of Biochemistry & Biophysics, University of Rochester Medical Center , Rochester, New York 14642, United States.
2
Center for RNA Biology, University of Rochester Medical Center , Rochester, New York 14642, United States.
3
Center for Integrated Research Computing, University of Rochester , Rochester, New York 14642, United States.
4
Department of Biostatistics & Computational Biology, University of Rochester Medical Center , Rochester, New York 14642, United States.

Abstract

The backbone dihedral parameters of the Amber RNA force field were improved by fitting using multiple linear regression to potential energies determined by quantum chemistry calculations. Five backbone and four glycosidic dihedral parameters were fit simultaneously to reproduce the potential energies determined by a high-level density functional theory calculation (B97D3 functional with the AUG-CC-PVTZ basis set). Umbrella sampling was used to determine conformational free energies along the dihedral angles, and these better agree with the population of conformations observed in the protein data bank for the new parameters than for the conventional parameters. Molecular dynamics simulations performed on a set of hairpin loops, duplexes and tetramers with the new parameter set show improved modeling for the structures of tetramers CCCC, CAAU, and GACC, and an RNA internal loop of noncanonical pairs, as compared to the conventional parameters. For the tetramers, the new parameters largely avoid the incorrect intercalated structures that dominate the conformational samples from the conventional parameters. For the internal loop, the major conformation solved by NMR is stable with the new parameters, but not with the conventional parameters. The new force field performs similarly to the conventional parameters for the UUCG and GCAA hairpin loops and the [U(UA)6A]2 duplex.

PMID:
28048939
PMCID:
PMC5312698
DOI:
10.1021/acs.jctc.6b00870
[Indexed for MEDLINE]
Free PMC Article

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