Evaluations of AMBER force field parameters by MINA approach for copper-based nucleases

Abstract

We describe the development of the AMBER force field parameters for 46 nucleases involving most kinds of copper nucleases with high DNA affinities and specificities by MINA approach that could evaluate accurate force constants for batch bonds/angles on the basis of energies of three adjacent lengths/angles geometries. The molecular mechanics (MM) and molecular dynamic simulations on adducts of the 21 representative copper-based nucleases with DNA are in excellent agreement with those of experimental results. Furthermore, to validate the evaluated parameters, the studied structures performed frequency analysis together with normal mode calculations in quantum mechanics and MM calculations. The force field parameters evaluated in this work provide an extension of AMBER force field, and the results of molecular dynamics simulations of adduct of copper nuclease and duplex DNA illustrate the potential utility of these parameters.