Estimating the Vertical Ionization Potential of Single-Stranded DNA Molecules.

Area of Science:

• Computational chemistry and biophysics
• Molecular biology and genetics

Background:

• DNA electronic properties, specifically sequence-dependent ionization potentials, facilitate long-range charge transport.
• This charge transport is implicated in vital cellular functions and disease-related DNA mutations.

Purpose of the Study:

• To achieve a molecular-level understanding of how DNA sequence influences electronic properties.
• To estimate the vertical ionization potential (vIP) for various DNA nucleobase sequences.

Main Methods:

• Utilized quantum chemistry calculations, including Møller-Plesset perturbation theory (MP2) and density functional theory (DFT) with various basis sets.
• Calculated vIPs for nucleobase stacks (1-4 bases) including guanine, adenine, thymine, cytosine, and methylated cytosine.
• Developed a recursive model, vIPer, to estimate vIP for any single-stranded DNA sequence using overlapping quadruplets.

Main Results:

• Identified MP2 with the 6-31G* basis set as the most accurate computational method by comparing with experimental data and genomic mutability frequencies.
• The vIPer model accurately estimates DNA sequence vIPs, showing good correlation with experimental oxidation potentials and DNA cleavage activities.
• vIPer is available as an open-source tool for sequence-dependent DNA electronic property analysis.

Conclusions:

• The vIPer model provides a reliable method for predicting DNA electronic properties based on sequence.
• This tool advances the understanding of DNA charge transport mechanisms and their biological implications.
• The findings support the link between DNA electronic properties, sequence, and cellular processes/diseases.