Moreover, some of the most important applications of force fields involve the simulation of as-yet undiscovered compounds, such as those under investigation for small molecule drug development, which may lie in new regions of chemical space. Small molecule force fields in wide use today include the general AMBER force field (GAFF), the CHARMM general force field (CGenFF), and the optimized potentials for liquid simulations force field (OPLS). These important tools have undergone continuous development, and current generations are applicable to a wide range of small molecules. Nonetheless, calculations of hydration free energies, partition coefficients, and other properties show that there is room for improvement in current general force fields. In addition, weaknesses in the small molecule component of the potential function likely account for some of the errors in calculations of noncovalent binding free energies relevant in host-guest chemistry and drug design. Improvements in force fields may come from the use of more and/or better reference data to optimize force field parameters, changes in the chemical typing rules used to assign parameters to atoms, and/or changes in the functional form of the force field. Exploring such improvements has traditionally involved considerable human input, and limitations in available computer power have made it difficult or impossible to carry out systematic explorations and optimizations. This has led to uncertainties in how exactly to go about attaining greater accuracy. For example, until it is clear how much accuracy can be achieved with a given functional form, it is impossible to ascertain whether or in what cases more accuracy is achieved by adding more detail and hence greater computational cost, e.g., by accounting explicitly for electronic polarizability. In addition, it is often unclear how the specific types and parameters of a given force field were arrived at, and this condition poses obstacles to reproducing and building on prior work. There is thus a need not only for improved force fields, but also for an infrastructure that will enable systematic exploration, optimization, and evaluation of new simulation force fields. Today, advances in software technology and increasing compute power make it possible to move toward the systematization and automation of force field generation.