Nucleotide insertion initiated by van der Waals interaction during polymerase beta DNA replication

TL;DR

This paper provides a theoretical analysis of nucleotide insertion during DNA replication, highlighting the role of van der Waals interactions and hydrogen bonds in the biochemical process without external energy input.

Contribution

It introduces a novel theoretical framework using van der Waals and hydrogen bond effects to explain nucleotide insertion in DNA replication.

Findings

Nucleotide insertion involves two interdependent biochemical steps.

Van der Waals interactions are key to the insertion process.

No external energy is required for the bond formation and breaking.

Abstract

We give unambiguous theoretical analyses and show that the exclusive biochemical reaction involved in a single nucleotide insertion into the DNA primer can be efficiently tracked using the renormalized van der Waals (vdW) interaction of a stronger type, the Hermansson blue-shifting hydrogen bond effect, and the Arunan composite hydrogen-vdW bond. We find that there are two biochemical steps involved to complete the insertion of a single base (cytosine) into the 3$'$ end of a DNA primer. First, the O3$'$ (from a DNA primer) initiates the nucleophilic attack on P$_{\alpha}$ (from an incoming dCTP), in response, O3$_{\alpha}$ (bonded to P$_{\alpha}$) interacts with H$'$ (bonded to O3$'$). These interactions are shown to be strongly interdependent and require the forming and breaking of P---O and H---O covalent bonds, which in turn imply that we do not need any external energy supply.