QM/MM-MD analysis of dissociation of Ag+ and H+ mediated cytidines

TL;DR

This study uses biased QM/MM molecular dynamics to analyze the dissociation mechanisms of cytidine complexes mediated by Ag+ or H+ ions, revealing detailed free energy profiles and dissociation pathways in solvent conditions.

Contribution

It introduces a comprehensive QM/MM-MD approach with thermodynamic integration to elucidate dissociation mechanisms of cytidine complexes, highlighting differences between Ag+ and H+ mediation.

Findings

Ag+ favors cisoid over transoid configurations.

Two energy minima exist before dissociation in all complexes.

Global minima differ from previous equilibrium geometries.

Abstract

We report a biased QM/MM molecular dynamics study of the dissociation process of cytidine-cytidine complexes mediated by Ag+ or H+ ions. We performed calculations under real solvent conditions and obtained the free energy profiles (FEP) by thermodynamic integration technique to give deep insights on the dissociation process. For all geometries corresponding to key points on FEP the noncovalent interaction descriptors (NCI) were calculated and the details of dissociation mechanism were revealed. Our findings by means of energy barrier analysis of FEP for Ag+ -mediated cytidines suggested more favorable cisoid over transoid configuration, in contrast to H+ mediated cytidines. The existence of two energy minima in FEP, local and global, in all Ag+ and H+ complexes before the dissociation transition state was revealed for the first time. We showed that the global minimum of dissociation profiles for both Ag+ -mediated cytidine isomers does not correspond to the previously obtained QM equilibrium geometries. Our results induce future studies of longer silver mediated DNA strands comprising cytosines by QM/MM-MD.