An extensible interface for QM/MM molecular dynamics simulations with AMBER

We present an extensible interface between the AMBER molecular dynamics (MD) software package and electronic structure software packages for quantum mechanical (QM) and mixed QM and classical molecular mechanical (MM) MD simulations within both mechanical and electronic embedding schemes. With this interface, ab initio wave function theory and density functional theory methods, as available in the supported electronic structure software packages, become available for QM/MM MD simulations with AMBER. The interface has been written in a modular fashion that allows straight forward extensions to support additional QM software packages and can easily be ported to other MD software. Data exchange between the MD and QM software is implemented by means of files and system calls or the message passing interface standard. Based on extensive tests, default settings for the supported QM packages are provided such that energy is conserved for typical QM/MM MD simulations in the microcanonical ensemble. Results for the free energy of binding of calcium ions to aspartate in aqueous solution comparing semiempirical and density functional Hamiltonians are shown to demonstrate features of this interface. © 2013 Wiley Periodicals, Inc.