Conformational control of TT dimerization in DNA conjugates. A molecular dynamics study

Area of Science:

• Photochemistry
• Molecular Biophysics
• DNA Damage and Repair

Background:

• Thymine-thymine (TT) photodimerization is a major DNA photolesion.
• The yield of photodimerization is influenced by DNA sequence and structure.
• Understanding these factors is crucial for DNA repair mechanisms and photoprotection strategies.

Purpose of the Study:

• To investigate the quantum yield of [2+2] and 6-4 photodimerization of TT steps in diverse DNA structures.
• To determine the context dependence of photodimerization yield, particularly in DNA hairpins.
• To develop and validate a theoretical model for predicting dimerization yields based on DNA structure.

Main Methods:

• Experimental measurement of quantum yields for photodimerization in DNA conjugates.
• Theoretical modeling using CASSCF (Complete Active Space Self-Consistent Field) electronic structure calculations.
• Analysis of geometric constraints, specifically inter-double bond distance (d and g) and dihedral angles.

Main Results:

• The study examined DNA structures including dT(20), dA(20)dT(20), and alkane-linked hairpins.
• For [2+2] photodimerization, a distance constraint (d < 3.52 Å) accurately predicts yield trends.
• For 6-4 photodimerization, a distance constraint (g < 2.87 Å) with no dihedral angle constraint provides accurate yield predictions.

Conclusions:

• DNA structure significantly impacts the quantum yield of TT photodimerization.
• Inter-double bond distance is the primary geometric determinant for both [2+2] and 6-4 photodimerization yields.
• The developed theoretical model successfully describes the observed trends in dimerization yield across different DNA structures.