Molecular Docking and Dynamics of CePNKP Phosphatase Binding to the ss-5-Mer TCCTC

Abstract

Polynucleotide kinase/phosphatase (PNKP) is a DNA repair enzyme found in mammals, which recognizes and repairs DNA backbone breaks with 3'-phosphate and 5'-hydroxyl ends. DNA can be damaged by ionizing radiation, chemical agents and enzymatic action. The phosphatase domain of PNKP recognizes the 3'-phosphate group, excises it, and replaces it with a 3'-hydroxyl group, thereby making the 3'-end ready for the action of a ligase that completes the DNA strand. In this work, the single-stranded 5-mer TCCTC sequence was docked to the phosphatase domain of the C. elegans PNKP using the Modeller interface implemented in the UCSF Chimera software, taking into account the crystallographic information available. The structure of the complex was subject to a classical molecular dynamics protocol using Gromacs. Molecular dynamics is a computer simulation technique that allows us to compute dynamic and thermodynamic properties to determine the physical interaction between the PNKP phosphatase and the ssDNA.

Department: Physical Sciences

Faculty Mentor: Dr. Jorge Llano