Conformational and energetic properties of pyrrolidinyl PNA-DNA duplexes: A molecular dynamics simulation

Abstract

The binding capability of pyrrolidinyl peptide nucleic acids (PNAs) to DNA have been studied experimentally, also the high affinity and sequence specificity were reported. However, to date a detailed understanding of these properties is unclear due to a lack of crystallographic data. In this work, molecular dynamics (MD) simulations of pyrrolidinyl PNA with different stereochemistry, (2′R,4′R)- and (2′R,4′S)-prolyl-(1S,2S)-2-aminocyclopentanecarboxylic acid (namely acpcPNA and epi-acpcPNA, respectively), binding to DNA were performed. MD simulations of three different forms (A-, B- and P-forms) were conducted to investigate the probable duplex conformation, which revealed that the MD structures were close to B-type duplex. It was found that acpcPNA and epi-acpcPNA backbones play a minor role in the hydrogen bond geometry of base pair, however, these greatly influence the interactions between PNA and DNA strands, leading to the differences in duplex stability. The calculated binding free energy revealed the higher thermodynamic stability of acpcPNA-DNA compared to epi-acpcPNA-DNA system, which is in good agreement with published experimental data. This work offers new insights into the conformational and energetic properties of pyrrolidinyl PNA-DNA duplexes at a molecular level.