Interaction between thymine dimer and flavin-adenine dinucleotide: a DFT and direct ab initio molecular dynamics...

Area of Science:

• Computational Chemistry
• Biochemistry
• Molecular Dynamics

Background:

• Thymine dimers (T)2 are DNA lesions.
• Photoenzymes, utilizing flavin adenine dinucleotide (FADH(-)), are involved in DNA repair.
• The precise mechanism of FADH(-)-mediated repair remains incompletely understood.

Purpose of the Study:

• To investigate the interaction between FADH(-) and thymine dimers (T)2.
• To elucidate the electron transfer mechanism in thymine dimer repair.
• To determine the dynamics of bond breaking and formation during repair.

Main Methods:

• Density Functional Theory (DFT) calculations for ground and excited states.
• Direct ab initio molecular dynamics (MD) simulations at HF/3-21G(d) and B3LYP/6-31G(d) levels.
• Analysis of charge distribution and reaction pathways.

Main Results:

• Calculated charges for FADH(-) and (T)2 at ground state were -0.9 and -0.1, respectively.
• Photoirradiation induced electron transfer from FADH(-) to (T)2 at the excited state.
• Electron capture by (T)2 led to elongation and preferential breaking of the C5-C5' bond within 100-150 fs.

Conclusions:

• The repair of thymine dimers by photoenzymes occurs efficiently via electron transfer from FADH(-).
• Molecular dynamics simulations provide insights into the ultrafast repair mechanism.
• This study confirms the critical role of electron transfer in FADH(-)-mediated DNA repair.