Molecular dynamics simulation of the preferred conformations of 2-thiouridine in aqueous solution

Abstract

Transfer RNA (tRNA) molecules display a large diversity of posttranscriptionally modified nucleosides at the anticodon wobble at position 34 and 3′ to the anticodon triplet at position 37. Some of these modifications appear to play an important role in the recognition of the correct codon on the ribosome. It has been suggested that these modifications work by regulating the conformational rigidity/flexibility of the nucleosides at those positions. We present here the results of a molecular dynamics study where we compare the conformational characteristics of uridine and 2-thiouridine in aqueous solution. We find that a newly derived parameter set for thio-modified uridines for the CHARMM27 force field for nucleic acids correctly reproduces the experimental observations. We also found that replica exchange molecular dynamics method with generalized Born molecular volume implicit solvent approximation reproduces the experimental observations at a much less computational effort and therefore may be considered as a promising method for simulating larger systems such as ribosome.