Optimization of an AMBER force field for the artificial nucleic acid, LNA, and benchmarking with NMR of L(CAAU).

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

SUBMITTER: Condon DE 

PROVIDER: S-EPMC3917691 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature