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 molecules interacting with a guanine base lead to a hypothesis that urea molecules along with water are able to form cage-like structures capable of trapping nucleic acid bases in extrahelical states by forming both hydrogen bonded and dispersion interactions, thereby contributing to the unfolding of RNA in the presence of urea in aqueous solution.

First examples of racemization of tetrahedral tetracoordinated centers via a planar transition state or an intermediate structure.

An understanding of the determinants of the thermal stability of thermostable proteins is expected to enable design of enzymes that can be employed in industrial biocatalytic processes carried out at high temperatures. A major factor that has been proposed to stabilize thermostable proteins is the high occurrence of salt bridges. The current study employs free energy calculations to elucidate the thermodynamics of the formation of salt bridge interactions and the temperature dependence, using acetate and methylguanidium ions as model systems. Three different orientations of the methylguanidinium approaching the carboxylate group have been considered for obtaining the free energy profiles. The association of the two ions becomes more favorable with an increase in temperature. The desolvation penalty corresponding to the association of the ion pair is the lowest at high temperatures. The occurrence of bridging water molecules between the ions ensures that the ions are not fully desolvated, and this could provide an explanation for the existence of internal water molecules in thermostable proteins reported recently. The findings provide a detailed picture of the interactions that make ion pair association at high temperatures a favorable process, and reaffirm the importance of salt bridges in the design of thermostable proteins.

We for the first time shown that transition between (R) and (S) stereoisomers via a planar transition state or an intermediate structure without having to break a bond is possible. Rigorous theoretical calculations have been used to study this novel phenomenon and to characterize the energetic, structure, dynamic and kinetic properties.

We for the first time shown that transition between (R) and (S) stereoisomers via a planar transition state or an intermediate structure without having to break a bond is possible. Rigorous theoretical calculations have been used to study this novel phenomenon and to characterize the energetic, structure, dynamic and kinetic properties.