Modeling condensed-phase chemistry through molecular dynamics simulation

Advances in computational power have greatly facilitated the successful implementation of large-scale computer simulations of biological assemblies and complex condensed phases. Researchers have developed numerous simulation techniques, but many of these share, at their core, the so-called molecular dynamics (MD) paradigm to simulate such systems. (See the “Molecular Dynamics in a Nutshell” sidebar for more specifics.) This article does not go into the details involving viable system sizes and allowable magnitudes of the time step in MD simulations. Suffice it to say that to model complex condensed phases using MD simulation requires approximately 1,000 to one million molecules examined over the course of multiple nanoseconds with a time step on the order of 0.001 to 0.002 picoseconds. This situation is already computationally daunting. Regardless, one goal is to extend the boundaries of accessible systems to include chemical reactions within the MD simulations. Unfortunately, this apparently logical extension to the MD method turns out to involve almost a complete restructuring of the method; in the instance that we let particles create and destroy chemical bonds, a new approach is necessary to simulate the systems. To perform an MD simulation of a reactive system, we require an atomistic model potential energy surface (PES), or force field. The PES will contain the information required for molecules to move, rotate, and translate as well as react with one another to form new species. This article describes methods for simulating protonated liquid water and condensed-phase reaction dynamics, in which the commonly used multi-atom empirical force fields are inadequate. We discuss two approaches that generate a specific PES that we can use in an MD simulation. The first is the multistate empirical valence bond (MS-EVB) approach to study the dynamics of excess protons in condensed media, including water and biological systems. The second is the ab initio-based atom-centered density matrix propagation (ADMP) method.