biostudies-literatureKasavajhala KDepartment of Biotechnology , Ministry of Science and TechnologyNational Institutes of HealthNIGMS NIH HHS3755-61https://www.ebi.ac.uk/biostudies/studies/S-EPMC4352126biostudies-literatureUnknown119(9)Urea has long been used to investigate protein folding and, more recently, RNA folding. Studies have proposed that urea denatures RNA by participating in stacking interactions and hydrogen bonds with nucleic acid bases. In this study, the ability of urea to form unconventional stacking interactions with RNA bases is investigated using ab initio calculations (RI-MP2 and CCSD(T) methods with the aug-cc-pVDZ basis set). A total of 29 stable nucleobase-urea stacked complexes are identified in which the intermolecular interaction energies (up to -14 kcal/mol) are dominated by dispersion effects. Natural bond orbital (NBO) and atoms in molecules (AIM) calculations further confirm strong interactions between urea and nucleobases. Calculations on model systems with multiple urea and water moleculeThe journal of physical chemistry. BDispersion interactions between urea and nucleobases contribute to the destabilization of RNA by urea in aqueous solution.PMC4352126R29 GM051501GM051501R01 GM051501Kasavajhala KPatil IBikkina SMacKerell ADPriyakumar UDfalseDispersion interactions between urea and nucleobases contribute to the destabilization of RNA by urea in aqueous solution.Urea has long been used to investigate protein folding and, more recently, RNA folding. Studies have proposed that urea denatures RNA by participating in stacking interactions and hydrogen bonds with nucleic acid bases. In this study, the ability of urea to form unconventional stacking interactions with RNA bases is investigated using ab initio calculations (RI-MP2 and CCSD(T) methods with the aug-cc-pVDZ basis set). A total of 29 stable nucleobase-urea stacked complexes are identified in which the intermolecular interaction energies (up to -14 kcal/mol) are dominated by dispersion effects. Natural bond orbital (NBO) and atoms in molecules (AIM) calculations further confirm strong interactions between urea and nucleobases. Calculations on model systems with multiple urea and water molecule2015-01-01T00:00:00Z2015 Mar2025-04-21T18:28:02.733Z2019-03-27T01:47:45ZS-EPMC43521262566875710.1021/jp512414f