inevitably comes with a decrease in accuracy for representing any particular subclass of molecules. Users are repeatedly warned in Mackerell's website not to use the CGenFF parameters for molecules for which specialized force fields already exist (as mentioned above for proteins, nucleic acids, etc.). CHARMM also includes polarizable force fields using two approaches. One is based on the fluctuating charge (FQ) model, also termed Charge Equilibration (CHEQ). The other is based on the Drude shell or dispersion oscillator model. Parameters for all of these force fields may be downloaded from the Mackerell website for free. Molecular dynamics program The CHARMM program allows for generating and analysing a wide range of molecular simulations. The most basic kinds of simulation are minimizing a given structure and production runs of a molecular dynamics trajectory. More advanced features include free energy perturbation (FEP), quasi-harmonic entropy estimation, correlation analysis and combined quantum, and quantum mechanics - molecular mechanics (QM/MM) methods. CHARMM is one of the oldest programs for molecular dynamics. It has accumulated many features, some of which are duplicated under several keywords with slight variants. This is an inevitable result of the many outlooks and groups working on CHARMM worldwide. The changelog file, and CHARMM's source code, are good places to look for the names and affiliations of the main developers. The involvement and coordination by Charles L. Brooks III's group at the University of Michigan is salient. Software history Around 1969, there was considerable interest in developing potential energy functions for small molecules. CHARMM originated at Martin Karplus's group at Harvard. Karplus and his then graduate student Bruce Gelin decided the time was ripe to develop a program that would make it possible to take a given amino acid sequence and a set of coordinates (e.g., from the X-ray structure) and to use this information to calculate the energy of the system as a function of the atomic positions. Karplus has acknowledged the importance of major inputs in the development of the (at the time nameless) program, including: Schneior Lifson's group at the Weizmann Institute, especially from Arieh Warshel who went to Harvard and brought his consistent force field (CFF) program with him Harold Scheraga's group at Cornell University Awareness of Michael Levitt's pioneering energy calculations for proteins In the 1980s, finally a paper appeared and CHARMM made its public début. Gelin's program had by then been considerably restructured. For the publication, Bob