Poster abstracts
Poster number 96 submitted by Alan Mlotkowski
Theoretical pKa calculations of modified purine nucleobases using explicit waters and a polarizable Ccontinuum model
Alan J. Mlotkowski (Department of Chemistry, Wayne State University), Evan Jones (Department of Chemistry, Wayne State University), Sebastien Hebert (Department of Chemistry, Wayne State University), H. Bernhard Schlegel (Department of Chemistry, Wayne State University), John SantaLucia, Jr (Department of Chemistry, Wayne State University), Christine S. Chow (Department of Chemistry, Wayne State University)
Abstract:
There are numerous modified nucleobases, which are believed to play roles in fine-tuning structure and function of various RNA molecules. Modifications of nucleobases have a wide range of effects including participating in regulation of expression and response to stress in the cell. Despite a growing wealth of knowledge, specific details about modifications are still not known. The pKa value is a defining characteristic of nucleobases, which is used to understand base-pairing energetics of modified nucleobases. Purine nucleobases and their modifications contain a minimum of two protonation/deprotonation sites that have unique pKa values. Modifications on nucleobases affect the pKa values, resulting in a change of nucleobase behavior. In this study, we determined the pKa values of 19 modified purine nucleobases by performing calculations with the Gaussian 16 program using the B3LYP/6-31+G(d,p) method with a combination of implicit-explicit solvation. This method involved the use of explicit water molecules forming hydrogen bonds with the nucleobases surrounded by an implicit solvation field. The pKa values were calculated from the change in the free energy between protonated and deprotonated forms of the nucleobases and the energy of the solvated proton. By using this approach, we have determined that a single modification can change the pKa value of protonation/deprotonation site on a purine nucleobase by as much as 4.0 units when compared to the unmodified purine nucleobase.
Keywords: modification, pka, compuational