Computational study of uracil tautomeric forms in the ribosome : the case of uracil and 5-oxyacetic acid uracil in the first anticodon position of tRNA

• Main Authors: Hartono, Yossa Dwi, Ito, Mika, Villa, Alessandra, Nilsson, Lennart
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2019
• Subjects: Uracil; Science::Biological sciences; Ribosome
• Online Access: https://hdl.handle.net/10356/106400; http://hdl.handle.net/10220/49608
• Institution: Nanyang Technological University

Tautomerism is important in many biomolecular interactions, not least in RNA biology. Crystallographic studies show the possible presence of minor tautomer forms of transfer-RNA (tRNA) anticodon bases in the ribosome. The hydrogen positions are not resolved in the X-ray studies, and we have used ab initio calculations and molecular dynamics simulations to understand if and how the minor enol form of uracil (U), or the modified uracil 5-oxyacetic acid (cmo5U), can be accommodated in the tRNA–messenger-RNA interactions in the ribosome decoding center. Ab initio calculations on isolated bases show that the modification affects the keto–enol equilibrium of the uracil base only slightly; the keto form is dominant (>99.99%) in both U and cmo5U. Other factors such as interactions with the surrounding nucleotides or ions would be required to shift the equilibrium toward the enol tautomer. Classical molecular simulations show a better agreement with the X-ray structures for the enol form, but free energy calculations indicate that the most stable form is the keto. In the ribosome, the enol tautomers of U and cmo5U pair with a guanine forming two hydrogen bonds, which do not involve the enol group. The oxyacetic acid modification has a minor effect on the keto–enol equilibrium.