Poster Presentation 2014 International Biophysics Congress

FIREBALL/AMBER: QM/MM method for biomolecular systems (#527)

Jesús Mendieta-Moreno 1 , Paulino Gomez-Puertas 2 , Jesús Mendieta 2 , José Ortega 1
  1. Theoretical Condensed Matter Physic, Universidad Autónoma de Madrid, Madrid, Spain
  2. Molecular Modelling Group, Centro de Biología Molecular Severo Ochoa, Madrid, Spain

In recent years, quantum mechanics/molecular mechanics (QM/MM) methods have become an important computational tool for the study of chemical reactions and other processes in biomolecular systems. Because of the complexity of biomolecules and the desire to achieve converged sampling, it is important that the QM method presents a good balance between accuracy and computational efficiency. Here, we report on the implementation of a QM/MM technique that combines a DFT approach specially designed for the study of complex systems using first-principles molecular dynamics simulations (FIREBALL) with the AMBER force fields and simulation programs [1].

We also present the application of this method, using DFT QM/MM molecular dynamics techniques, to study two different enzymatic reactions: phosphodiester bond cleavage by RNase A and DNA polymerization by HIV reverse transcriptase. In particular, the computational efficiency of our approach allowed the generation of free-energy surface maps to explore the large conformational space for the reactions, thus permitting a detailed analysis of alternative pathways. 

  1. Jesús I. Mendieta-Moreno, Ross C. Walker, Paulino Gómez-Puertas, James P. Lewis, Jesús endieta and José Ortega, “FIREBALL/AMBER: An efficient local-orbital DFT QM/MM method for biomolecular systems”, Journal of Chemical Theory and Computation, DOI: 10.1021/ct500033w, 2014.