Conformational, Molecular, Spectral and Binding Properties of Zn(II)-Coordinated Glycol Nucleic Acid Monophosphate: A DFT, Docking and Molecular Dynamics Assessment

Glycol Nucleic Acid (GNA), the simplest xeno nucleic acid (XNA) featuring a propylene glycol unit, has attracted considerable attention due to its emerging therapeutic and biotechnological applications. The conformational, molecular, and spectral properties of the GNA nucleotide conformers containing cytosine, thymine, and uracil in both free and Zn(II)-coordinated forms were investigated for the first time using B3LYP/6-311 + + G(d,p). Further, binding characteristics of the metal coordinated entities with KRAS protein were investigated through docking and molecular dynamics simulations. The results suggest that incorporation of Zn(II) into the nucleobases induces significant deviations in the system’s electronic landscape including dipole moments, HOMO-LUMO gaps, chemical hardness, and electrophilicity. Docking and MD simulations highlight significant interactions of metal-GNA ligand with KRAS residues (ASP30, VAL29, GLU31), including characteristic hydrogen bonding patterns across the simulated replicas. Overall, the results presented herein are expected to provide valuable insights into the research field of engineered genetic materials.