Poster abstracts

Poster number 141 submitted by Evan Jones

Theoretical pKa Calculations of Modified Nucleobases using Explicit Waters and a Polarizable Continuum Model

Evan L Jones (Wayne State University, Chemistry), Alan Mlotkowski (Wayne State University, Chemistry), Sebastain Hebert (Wayne State University, Chemistry), H. Bernhard Schlegel (Wayne State University, Chemistry), John SantaLucia, Jr. (Wayne State University, Chemistry), Christine S. Chow (Wayne State University, Chemistry)

Abstract:
Modified nucleobases are often responsible for key structural roles and are found in functionally important regions of RNA. Several nucleobase modifications such as methylations are dynamically regulated in nature with each playing a different regulatory role. The detailed characteristics of modifications are still poorly understood. One important feature of a nucleobase that could impact structure and function is the pKa value. Nucleobases contain one or more protonation/deprotonation sites, all with unique pKa values. Modifications to nucleobases lead to changes in the protonation/deprotonation sites. To fully understand the impacts of nucleobase modifications, the pKa values of modified nucleobases first have to be determined. Of more than 100 known nucleobase modifications, only a small percentage has reported pKa values. In this study, we determined the pKa values of various modified nucleobases from RNA and compared them to their unmodified counterparts by performing Gaussian calculations with a B3LYP 6-31 +G(d,p) basis set.(1) This method involved the use of explicit water molecules surrounded by an implicit solvation field along with a methyl group that is substituted in the place of the ribose sugar. This approach indicates that modifications have a wide range of effects on the pKa values of nucleobase functional groups. Understanding the pKa values of modified nucleobases will give insight into the specific structural impact 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: RNA Modifications, Computational Chemistry