Spin‐projected QM/MM Free Energy Simulations for Oxidation Reaction of Guanine in B−DNA by Singlet Oxygen
| Autor: | Yu Takano, Toru Saito |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Materials science
Guanine 02 engineering and technology Activation energy Electronic structure 010402 general chemistry 01 natural sciences Molecular physics Spin contamination Article QM/MM chemistry.chemical_compound Physical and Theoretical Chemistry spin contamination Density Functional Theory Spin-½ Singlet Oxygen Singlet oxygen Diradical QM/MM MD Articles DNA 021001 nanoscience & nanotechnology Atomic and Molecular Physics and Optics 0104 chemical sciences chemistry Models Chemical Thermodynamics Density functional theory oxidation reaction 0210 nano-technology DNA B-Form Oxidation-Reduction |
| Zdroj: | Chemphyschem |
| ISSN: | 1439-7641 1439-4235 |
| Popis: | Guanine is the most susceptible base to oxidation damage induced by reactive oxygen species including singlet oxygen (1O2, 1Δg). We clarify whether the first step of guanine oxidation in B−DNA proceeds via either a zwitterionic or a diradical intermediate. The free energy profiles are calculated by means of a combined quantum mechanical and molecular mechanical (QM/MM) method coupled with the adaptive biasing force (ABF) method. To describe the open‐shell electronic structure of 1O2 correctly, the broken‐symmetry spin‐unrestricted density functional theory (BS−UDFT) with an approximate spin projection (AP) correction is applied to the QM region. We find that the effect of spin contamination on the activation and reaction free energies is up to ∼8 kcal mol−1, which is too large to be neglected. The QM(AP−ULC−BLYP)/MM‐based free energy calculations also reveal that the reaction proceeds through a diradical transition state, followed by a conversion to a zwitterionic intermediate. Our computed activation energy of 5.2 kcal mol−1 matches experimentally observed range (0∼6 kcal mol−1). Realistic (free energy) profile: We demonstrate how singlet oxygen reacts with guanine in B−DNA by means of the spin‐projected QM(AP−ULC−BLYP)/MM free energy simulations. The present approach gives a realistic free energy profile, which agrees well with experimental findings. The rate‐limiting syn‐addition of 1O2 is found to proceed via a diradical transition state, followed by the smooth conversion from the open‐shell surface to the closed‐shell one. |
| Databáze: | OpenAIRE |
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