Active site structure and reaction mechanism of DNA polymerase β studied by molecular dynamics simulation and QM/MM method

COMP 172

Ping Lin,, College of Chemistry and Chemical Engineering, Donghua University, 1882,West Yan-an Road, Shanghai, 200051, China and Lee G. Pedersen,, Department of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Earlier theoretical and experimental studies have found that the two metal ions play a vital role in organizing the active site toward the catalytic reaction. In this study, we investigated the general features of the ternary structure of DNA polymerase β-(primer-template) DNA-incoming nucleoside triphosphate (dNTP) using classic molecular dynamic simulation, especially the active site structure and the role of the metal ions. Our calculations indicate that the two Mg2+ ions are important in bringing the dNTP and 3'-OH group of the primer in places for the nucleophilic attack. The active site structures under different metal coordination conditions were also investigated using combined quantum mechanics and molecular mechanics method (QM/MM), and a detailed reaction mechanism is proposed based on current study.