Molecular Dynamics Simulation of Melting of the DNA Duplex with Silver-Mediated Cytosine–Cytosine Base Pair

Abstract

Metal-mediated base pairs in DNA double helix molecules open up broad opportunities for biosensors based on DNA clusters with silver due to their low toxicity and applicability in drug design. Despite intensive experimental and computational research, molecular mechanisms of stabilization of a double helix by silver-mediated base pairs are mainly unknown. We conducted all-atom molecular dynamics simulations of a dodecameric DNA double helix (sequence 5′-TAGGTCAATACT-3′-3′ATCCACTTATGA-5′) with either cytosine–cytosine or cytosine–Ag+–cytosine mismatch in the center of the duplex. We extended the previously proposed set of interaction parameters for a silver ion in the silver-mediated pair in order to allow for its dissociation. With this new potential, we studied how the addition of a silver ion could stabilize a DNA double helix containing a single cytosine–cytosine mismatch. In particular, we found out that the helix with cytosine–Ag+–cytosine mismatch has a greater melting temperature than the helix with cytosine–cytosine one. This stabilization effect of the silver ion is in qualitative agreement with experimental data. The central region of the duplex with cytosine–Ag+–cytosine mismatch (unlike with cytosine–cytosine mismatch) is stable enough to prevent bubble formation at moderate temperatures during melting. The results of this simulation can be used to devise novel metal-mediated DNA structures.