High Performance Liquid historical development

The focus in development of the OPLS-UA model was on the non-bonded parameters, which historically had been the most problematic, and the new approach was to perform large numbers of Monte Carlo statistical mechanics simulations of pure liquids for their refinement. This advance was made possible by increases in computer resources and the development of flexible, efficient software, namely, the BOSS program and its predecessors, that allowed rapid setup of simulations for new systems. The key point was that a principal application of such force fields was in condensed-phase simulations including protein dynamics, and testing of the force fields on prediction of well-characterized condensed-phase properties was needed. Minimally, reproduction of liquid densities and heats of vaporization provides some confidence in both the size of the molecules and the strengths of their intermolecular interactions. Furthermore, these quantities are obtained from both experiment and simulation with high precision. 

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