Theoretical investigation into the position-dependent influence of l-deoxynucleotides in the template strand on T7 RNA polymerase transcription activity

Abstract

In this study, we used molecular dynamics simulations to investigate the position-dependent effect of L-deoxynucleosides in the template strand on RNA transcription, based on structural analysis of DNA–RNA hybrids. We created a concise model, referred to as the Ramachandran-like plot for nucleic acids, to elucidate the structural information of DNA–RNA hybrids, which included the puckering angles, backbone dihedral angles, base pairs, helical parameters, and structural deviations and dynamics of sugar molecules. This plot derived several types of structural models of DNA–RNA hybrids containing L-deoxynucleotides at specific positions, via distortion, dislocation, π–π stacking, and non-Watson–Crick base pairing. The data showed that L-deoxynucleosides twisted towards downstream N/T strands in distorted and dislocated structures via interactions involving certain hydrogen bonds between L-deoxynucleosides and downstream bases and presented structural characteristics during non-Watson–Crick base pairing and π–π stacking that were similar to those observed during Watson–Crick base pairing, which were used to infer whether RNA transcription was inhibited.