A TD-DFT-Based Study on the Attack of the OH center dot Radical on a Guanine Nucleotide

Author(s)

Santiago, Joao ; de Faria, Jhaison C. ; San-Miguel, Miguel ; Bernal, Mario A.

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 17, p. 9-pg., 2022-09-01.

Abstract

Heavy charged particles induce severe damage in DNA, which is a radiobiological advantage when treating radioresistant tumors. However, these particles can also induce cancer in humans exposed to them, such as astronauts in space missions. This damage can be directly induced by the radiation or indirectly by the attack of free radicals mainly produced by water radiolysis. We previously studied the impact of a proton on a DNA base pair, using the Time Dependent-Density Functional Theory (TD-DFT). In this work, we go a step further and study the attack of the OH center dot radical on the Guanine nucleotide to unveil how this molecule subsequently dissociates. The OH center dot attack on the H1 ', H2 ', H3 ', and H5 ' atoms in the guanine was investigated using the Ehrenfest dynamics within the TD-DFT framework. In all cases, the hydrogen abstraction succeeded, and the subsequent base pair dissociation was observed. The DNA dissociates in three major fragments: the phosphate group, the deoxyribose sugar, and the nitrogenous base, with slight differences, no matter which hydrogen atom was attacked. Hydrogen abstraction occurs at about 6 fs, and the nucleotide dissociation at about 100 fs, which agrees with our previous result for the direct proton impact on the DNA. These calculations may be a reference for adjusting reactive force fields so that more complex DNA structures can be studied using classical molecular dynamics, including both direct and indirect DNA damage. (AU)

• FAPESP's process: 20/02348-8 - Calibration of the REAX force field for the proton-atom interactions
• Grantee: João Guilherme Rivera Santiago
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/15316-7 - Study of the interaction of heavy charged particles with DNA using computational methods
• Grantee: Mario Antonio Bernal Rodriguez
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 15/21873-8 - Establishment and application of methodologies for optimizing imaging techniques in digital radiology
• Grantee: Alessandra Tomal
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/08647-7 - Developments of X-ray characterization techniques and application in quantitative neuroscience
• Grantee: Jean Rinkel
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/51594-2 - Development of a computational system for the simulation of the interaction of ionizing radiations with the human genetic material
• Grantee: Mario Antonio Bernal Rodriguez
• Support Opportunities: Research Grants - Young Investigators Grants