MOLECULAR DYNAMICS OF THYMINE DIMER LESIONED DNA AND OF T4 ENDONUCLEASE V : ROLE OF ELECTROSTATIC ENERGY IN RECOGNITION PROCESS

Abstract Specific recognition mechanism by which repair enzyme recognizes the damaged site on DNA molecules is necessary for its correct repair. T4 endonuclease V is a DNA repair enzyme from bacteriophage T4 that catalyzes the first reaction step of the pyrimidine thymine dimer (TD) repair pathway. To obtain insight into the correct recognition of the TD site, the molecular dynamics (MD) simulations of the native DNA, DNA containing TD and the T4 endonuelease V were performed for 600 ps individually for each molecule. Simulations were analysed to determine the role of electrostatic interaction in the recognition process. It is found that electrostatic energies calculated for amino acids of the enzyme have positive values of around +15 kcal/mol. The electrostatic energy of the TD site has a negative value of approximately 9 kcal/mol, different form the nearly neutral value of the respective thymines site of the native DNA. The electrostatic interaction of the TD site with surrounding water environment differs from the electrostatic interaction of other nucleotides. Differences found between the TD site and respective thymines site of native DNA indicate that the electrostatic energy is an important factor contributing to proper recognition of the TD site during the scanning process in which enzyme scans the DNA.