Nuclear Magnetic Resonance of Single-Stranded RNAs and DNAs of CAAU and UCAAUC as Benchmarks for Molecular Dynamics Simulations

Abstract

RNA and DNA are rapidly emerging as targets for therapeutics and as potential frameworks for nanotechnology. Accurate methods for predicting and designing structures and dynamics of nucleic acids would accelerate progress in these and other applications. Suitable approximations for modeling nucleic acids are being developed but require validation against disparate experimental observations. Here, nuclear magnetic resonance spectra for RNA and DNA single strands, CAAU and UCAAUC, are used as benchmarks to test molecular dynamics simulations with AMBER force fields OL3 and ROC-RNA for RNA and BSC1 for DNA. A detailed scheme for making comparisons is also presented. The results reflect recent progress in approximations and reveal remaining challenges.

MD simulations reveal the basis for dynamic assembly of Hfq–RNA complexes

“…Supporting information-This article contains supporting information (6,21,35,36,57,58,(70)(71)(72)(73)(74)(75)(76)(77) (Table S8).…”

Fine-Tuning of the AMBER RNA Force Field with a New Term Adjusting Interactions of Terminal Nucleotides

“…One test simulation of r(CAAU) TN was performed at temperature 275 K corresponding to the experimental conditions. [22][23][24]31 The same l values were applied resulting in effective solute temperature range from 275 K to ~460 K.…”

“…Conformation ensembles of TNs provide one of the key benchmarks for testing RNA ffs due to their small size and straightforward comparison of their simulations with solution experiments. [19][20][21][22][23][24][25][26][27][28][29][30][31] Obviously, any quantitative ff assessment is critically dependent on the convergence of structural populations because only well-converged simulations can provide unambiguous benchmark datasets. Nevertheless, contemporary simulation methods and hardware already allow to obtain sufficiently converged simulation ensembles for TNs.…”

Automatic learning of hydrogen-bond fixes in an AMBER RNA force field

“…For the tetramers we computed the agreement with previously published NMR data [65][66][67] using the same procedure as in Ref. 23…”

“…In particular, we tested two other tetramers (CAAU and UUUU), for which NMR data are available. CAAU is one of the most challenging tetramers [23][24][25]65,67,74,76,79,80 and shows a relatively large χ 2 of 5.37 with gHBfix19 24 as well as 5.0 when reweighting the simulations using gHBfix opt . The test simulation with gHBfix opt reduces the χ 2 value to 3.6, which is an improvement.…”