How proton transfer affects the helical parameters in DNA:DNA microhelices

Abstract

Proton transfer reactions are a widespread phenomenon in many areas of the life sciences and it is one of the origins of the spontaneous point mutations during DNA replication. Because of its importance, many studies have been reported on these reactions. However, the present work is the first one focused on the structural geometrical changes by double proton transfer (DPT). Thus, different Watson–Crick (WC) pairs were optimized first in a simple model with one nucleoside base pair, and in a microhelix form with three nucleoside base pairs. The canonical and few tautomeric forms were considered in DNA:DNA microhelices with A-type and B-type helical forms. The stability of these structures and how the DPT process affects the main geometrical parameters was analyzed, in particular the deformation of the helical parameters. The M06-2X DFT method was used for this purpose. The purine/pyrimidine ring in the keto form appears easier to be deformed than when it is in the enol form. The weaker WC base pair formed with mixed microhelices than with nucleobases alone and the significant deformation of the helical and backbone parameters with the DPT appears to complicate this process in microhelices. Communicated by Ramaswamy H. Sarma