Theoretical insights into water network of B-DNA duplex with Watson-Crick and Hoogsteen base pairing geometries

•MD simulations on three solvated B-DNA structures including base pairs in Watson-Crick and Hoogsteen pairing modes.•Model proposed to identify water molecules within the major and minor grooves of the DNA.•The major and minor grooves of B-DNA show distinctly different hydration properties.•Hoogsteen base pairing significantly alters the H-bond network within both grooves compared to Watson-Crick base pairing. Solvation is essential for the proper structure and functioning of biomolecules. It has a major role in establishing the B-form as the dominant structure of DNA and strongly affects its biological functions. In our genome, two modes of base pairing (Watson-Crick (WC) and Hoogsteen (HG)) exist in equilibrium and are related to the functional properties of the DNA including ligand recognition and gene regulation. Here, we use molecular dynamics simulation along with topological analysis of the H-bond network to investigate the hydration patterns of DNA structure with WC and HG base pairings. We showed that DNA most significantly disturbs the H-bonding properties of the first hydration shell and slightly the second shell compared to bulk water and that the water network is considerably different in the minor and major grooves. We found that HG base pairing leads to increased solvation of the major groove and a less ordered water structure in the minor groove accompanied with increasing hydrophobicity of the minor groove which could also contribute to the site recognition of specific DNA binding proteins. Our newly developed method to selectively study the solvation of the minor and major grooves opens the door to study in finer details the binding between various form of DNA and different ligands such drugs, RNA and proteins.