Our method develop efforts include condensed-phase geometry optimization and vibrational mode calculation and interpretation.

Adam Hixson has derived a rigorous, multiple-copy simulation algorithm that is formally equivalent to conventional classical molecular dynamics for an ensemble of systems, but may be used for rapid geometry optimizations. The derivation was inspired by locally enhanced sampling (LES) and is accomplished by starting from an ensemble of copies of the entire system and applying a point coordinate transformation to a large sub-system defined as the bath. After the transformation, each atom of the bath is described by one "major" pseudo-particle located at the average position of the ensemble of equivalent atoms and a set of "minor" pseudo-particles whose coordinates differ slightly from those of the major pseudo-particle. Neglecting Hamilton's equations of motion for the minor pseudo-particles gives the equations of motion for LES. Numerical tests indicate that the algorithm can recover exact molecular dynamics of the ensemble, conventional multiple-copy dynamics, or results of intermediate accuracy. Thus, the algorithm provides a rigorous basis for multiple-copy dynamics and resolves many of the uncertainties associated with their current implementations.

Figure V-1. The experimental vibrational frequencies of liquid water (solid trace) are compared with stick diagrams representing vibrational frequencies calculated by using principal component analysis (PCA) of QM/MM trajectories (called principal mode analysis), fast Fourier transforms (FFT), or the maximum entropy method (MEM).