Molecular simulations are widely used in drug design, materials design, and in the study of biophysical processes. Large systems, like biomolecules or even small molecules in solution, prove to be computationally difficult to simulate at the quantum mechanical (QM) level of theory. For this reason, classical empirical potential energy functions known as force fields are often used in place of quantum mechanics in order to efficiently simulate chemical and biological systems. General small force fields, such as the general AMBER force fields GAFF and GAFF2 , OPLS , CGenFF , and the Merck molecular force fields MMFF94 and MMFF94S , were built to model a wide variety of small organic molecules. These force fields are often fit to attempt to reproduce energies and geometries observed in QM calculations. However, when applied to new molecules, they have been observed to differ from both quantum mechanical calculations and from each other in predicted energies and optimized geometries for important areas of chemical space .