Back to Search
Start Over
Optimization of an AMBER force field for the artificial nucleic acid, LNA, and benchmarking with NMR of L(CAAU).
- Source :
-
The journal of physical chemistry. B [J Phys Chem B] 2014 Feb 06; Vol. 118 (5), pp. 1216-28. Date of Electronic Publication: 2014 Jan 24. - Publication Year :
- 2014
-
Abstract
- Locked Nucleic Acids (LNAs) are RNA analogues with an O2'-C4' methylene bridge which locks the sugar into a C3'-endo conformation. This enhances hybridization to DNA and RNA, making LNAs useful in microarrays and potential therapeutics. Here, the LNA, L(CAAU), provides a simplified benchmark for testing the ability of molecular dynamics (MD) to approximate nucleic acid properties. LNA χ torsions and partial charges were parametrized to create AMBER parm99_LNA. The revisions were tested by comparing MD predictions with AMBER parm99 and parm99_LNA against a 200 ms NOESY NMR spectrum of L(CAAU). NMR indicates an A-Form equilibrium ensemble. In 3000 ns simulations starting with an A-form structure, parm99_LNA and parm99 provide 66% and 35% agreement, respectively, with NMR NOE volumes and (3)J-couplings. In simulations of L(CAAU) starting with all χ torsions in a syn conformation, only parm99_LNA is able to repair the structure. This implies methods for parametrizing force fields for nucleic acid mimics can reasonably approximate key interactions and that parm99_LNA will improve reliability of MD studies for systems with LNA. A method for approximating χ population distribution on the basis of base to sugar NOEs is also introduced.
Details
- Language :
- English
- ISSN :
- 1520-5207
- Volume :
- 118
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The journal of physical chemistry. B
- Publication Type :
- Academic Journal
- Accession number :
- 24377321
- Full Text :
- https://doi.org/10.1021/jp408909t