Methods for combined ab initio/empirical forcefield molecular dynamics and ab initio studies of the azide ion in various solvents

Combined ab initio/empirical forcefield molecular dynamics (QM/MM) simulations are considered to be a promising technique for the study of condensed phase chemical reactions and enzyme catalysis at finite temperature. Given current computer technology, only small model systems of protein active sites and condensed phase chemical reactions are accessible for study with ab initio techniques. A method and code were developed for extending the Car-Parrinello ab initio molecular dynamic technique to study systems where some of the forces between atoms are derived from predefined potential functions. Techniques for the correct treatment of electrostatic interactions between empirical point charges and the electron density arising from the ab initio atoms are presented for two cases: (1) where the system is enclosed by a single simulation cell, and (2) where two simulation cells are defined, one to enclose the entire system and a second, smaller cell in which the electronic structure calculation is performed. For the case of two simulation cells, a second length scale was introduced into the plane wave based generalized gradient approximation to density functional theory. By doing so, the short-range, rapidly varying electron-electron and electron-atom interactions, in the region of space where the electrons are localized, can be treated using an appropriately large plane wave basis set, while the long-range, slowly-varying electron interactions with the empirical atoms can be treated using a small plane wave basis set. After developing the code and methods necessary for correctly and accurately calculating interactions between atoms described within the ab initio (QM) and the empirical (MM) methods, potentials that accurately describe interactions between QM and MM atoms were investigated. The first system to be studied was water at ambient conditions. An interaction potential was developed to accurately model the hydrogen bond donor and acceptor characteristics between water molecules described by GGA DFT and TIP3P parameters. In particular, effective pseudopotentials were fit, using the water dimer as the basis of parametrization, to the TIP3P oxygen and hydrogen models. Next, the treatment of systems in which the QM and MM regions reside in the same molecule was investigated. When a covalent bond connects the QM and MM regions, the monovalent carbon pseudopotential developed by Röthlisberger was used to truncate the electronic structure. It was then necessary to devise an appropriate electrostatic coupling scheme for treating pairs of QM and MM atoms involved in intramolecular interactions. The method for treating the electrostatics, and scalability of the code were verified through an application to a solvated protein system which contained a total of ≈30,000 atoms of which 79 where treated by the ab initio method. Car-Parrinello ab initio molecular dynamics simulations were used to study the azide ion in the gas phase, deuterated water, and the models of the active site of Human Carbonic Anhydrase. The calculated asymmetric stretch frequency of the azide ion was compared to the experimentally measured value for each of the three systems. Explanations for the large blue shift in this frequency were then proposed