Poster abstracts

Poster number 61 submitted by Evan Jones

Theoretical pKa determinations of modified nucleobases using an implicit-explicit solvation model

Evan Jones, Evan Jones (Department of Chemistry, Wayne State University), Sebastien Hebert, H. Bernhard Schlegel (Department of Chemistry, Wayne State University), John SantaLucia (Department of Chemistry, Wayne State University), Christine S. Chow (Department of Chemistry, Wayne State University)

Abstract:
Nucleobase modifications play an important role in modulating the structural characteristics of RNA. Common examples of modifications include methylation of nucleobases, which changes the electronic structure and introduces non-polar character. Due to our interest in higher-order RNA structure and function, the specific characteristics of modifications need to be determined. One characteristic, the pKa value, plays an important role in determining the strength of hydrogen-bonding interactions by a modified nucleotide. Nucleobases contain one or more sites that can undergo protonation/deprotonation, and modifications to the nucleobase may result in changes to the pKa values. For RNA base pairs to form, they must displace waters in the first solvation sphere. A qualitative approximation may be achieved by combining implicit and explicit solvation to mimic the properties of the first solvation sphere. In this study, we used ab initio quantum mechanical calculations using a B3LYP/6-31+g(d,p) level of theory and SMD implicit solvation model with explicit water molecules to simulate the first solvation sphere (1). Calculations were performed using the Gaussian 09 program to predict pKa values for modified nucleobases and compared the results to experimentally determined pKa values. This approach gives improved theoretical pKa values for unmodified nucleosides and demonstrates that modifications have a wide range of effects on the pKa values of functionalized nucleobases. Understanding the pKa values of modified nucleobases will give insight into the specific structural and energetic impacts of these modifications.

References:
Thapa, B; Schlegel, H. B.; Calculations of pKa's and Redox Potentials of Nucleobases with Explicit Waters and Polarizable Continuum Solvation. J. Phys. Chem. A, 2015, 119 (21), pp 5134-5144

Keywords: pKa, modified nucleobases