T7 RNA Polymerase Discriminates Correct and Incorrect Nucleoside Triphosphates by Free Energy.

ABSTRACT: RNA polymerase (RNAP) is the primary machine responsible for transcription. Its ability to distinguish between correct (cognate) and incorrect (noncognate) nucleoside triphosphates (NTPs) is important for fidelity control in transcription. In this work, we investigated the substrate selection mechanism of T7 RNAP from the perspective of energetics. The dissociation free energies were determined for matched and unmatched base pairs in the preinsertion complex using the umbrella sampling method. A clear hydrogen-bond-rupture peak is observed in the potential of mean force curve for a matched base pair, whereas no such peaks are present in the position of mean force profiles for unmatched ones. The free-energy barrier could prevent correct substrates from being separated from the active site.

SUBMITTER: Wu S 

PROVIDER: S-EPMC5937113 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature