title: fireball/amber: An Efficient Local-Orbital DFT QM/MM Method for Biomolecular Systems.
abstract: 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. In the QM/MM technique, the active region is described by means of QM calculations, while the remainder of the system is described using a MM approach. 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. We also present examples of the application of this QM/MM approach to three representative biomolecular systems: the analysis of the effect of electrostatic embedding in the behavior of a salt bridge between an aspartic acid and a lysine residue, a study of the intermediate states for the triosephosphate isomerase catalyzed conversion of dihydroxyacetone phosphate into glyceraldehyde 3-phosphate, and the detailed description, using DFT QM/MM molecular dynamics, of the cleavage of a phosphodiester bond in RNA catalyzed by the enzyme RNase A.
authors.affiliation: Departamento de Física Teórica de la Materia Condensada and Condensed Matter Physics Center (IFIMAC), Universidad Autónoma de Madrid , ES-28049 Madrid, Spain.|Molecular Modelling Group, Center of Molecular Biology "Severo Ochoa" (CSIC- UAM) , ES-28049 Madrid, Spain.|Biomol-Informatics SL, Campus UAM, ES-28049 Madrid, Spain.
authors.forename: Jesús I
authors.initials: JI
authors.lastname: Mendieta-Moreno
authors.affiliation: San Diego Supercomputer Center and Department of Chemistry and Biochemistry, University of California-San Diego, La Jolla, California 92093, United States.
authors.forename: Ross C
authors.initials: RC
authors.lastname: Walker
authors.affiliation: Department of Physics, West Virginia University , Morgantown, West Virginia 26506-6315, United States.
authors.forename: James P
authors.initials: JP
authors.lastname: Lewis
authors.affiliation: Molecular Modelling Group, Center of Molecular Biology "Severo Ochoa" (CSIC- UAM) , ES-28049 Madrid, Spain.
authors.forename: Paulino
authors.initials: P
authors.lastname: Gómez-Puertas
authors.affiliation: Molecular Modelling Group, Center of Molecular Biology "Severo Ochoa" (CSIC- UAM) , ES-28049 Madrid, Spain.|Biomol-Informatics SL, Campus UAM, ES-28049 Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Mendieta
authors.affiliation: Departamento de Física Teórica de la Materia Condensada and Condensed Matter Physics Center (IFIMAC), Universidad Autónoma de Madrid , ES-28049 Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Ortega