CHARMM

CHARMM (Chemistry at HARvard Macromolecular Mechanics) is the name of a widely used set of force fields for molecular dynamics as well as the name for the molecular dynamics simulation and analysis package associated with them.^[1][2] The CHARMM Development Project involves a network of developers throughout the world working with Martin Karplus and his group at Harvard to develop and maintain the CHARMM program. Licenses for this software are available, for a fee, to people and groups working in academia.

The commercial version of CHARMM, called CHARMm (note the lowercase 'm'), is available from Accelrys.

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CHARMM force fields

The CHARMM force fields for proteins include united-atom (sometimes called "extended atom") CHARMM19^[3], all-atom CHARMM22^[4] and its dihedral potential corrected variant CHARMM22/CMAP.^[5] In the CHARMM22 protein force field, the atomic partial charges were derived from quantum chemical calculations of the interactions between model compounds and water. Furthermore, CHARMM22 is parametrized for the TIP3P explicit water model. Nevertheless, it is frequently used with implicit solvents. Recently, a special version of CHARMM22/CMAP was reparametrized for consistent use with implicit solvent GBSW.^[6]

For DNA, RNA, and lipids, CHARMM27^[7] is used. Some force fields may be combined, for example CHARMM22 and CHARMM27 for the simulation of protein-DNA binding. Additionally, parameters for NAD+, sugars, fluorinated compounds, etc. may be downloaded. These force field version numbers refer to the CHARMM version where they first appeared, but may of course be used with subsequent versions of the CHARMM executable program. Likewise, these force fields may be used within other molecular dynamics programs that support them.

Charmm also includes polarizable force fields using two approaches. One is based on the Drude shell or dispersion oscillator model. ^[8][9] The other is based on the fluctuating charge (FQ) model, also known as Charge Equilibration (CHEQ). ^[10][11]

Charmm molecular dynamics program

The CHARMM program allows generation and analysis of a wide range of molecular simulations. The most basic kinds of simulation are minimization of 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 molecular mechanics (QM/MM) methods.

CHARMM is one of the oldest programs for molecular dynamics. It has accumulated a huge number of features, some of which are duplicated under several keywords with slight variations. This is an inevitable result of the large number of outlooks and groups working on CHARMM throughout the world. The changelog file as well as 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 Scripps Institute is very salient.

History of the program

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 (still 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 (CCF) program with him;
• Harold Scheraga's group at Cornell University; and
• 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 Bruccoleri came up with the name HARMM (HARvard Macromolecular Mechanics), but it didn't seem appropriate. So they added a C for Chemistry. Karplus said: "I sometimes wonder if Bruccoleri's original suggestion would have served as a useful warning to inexperienced scientists working with the program."^[12] CHARMM has continued to grow and the latest release of the executable program was made in August 2007 as CHARMM34b1.

Running CHARMM Under Unix/Linux

The general syntax for using the program is:

charmm < filename.inp > filename.out

charmm 

The actual name of the program (or script which runs the program) on the computer system being used.

filename.inp 

A text file which contains the CHARMM commands. It starts by loading the molecular topologies (top) and force field (par). Then one loads the molecular structures' Cartesian coordinates (e.g. from PDB files). One can then modify the molecules (adding hydrogens, changing secondary structure). The calculation section can include energy minimization, dynamics production, and analysis tools such as motion and energy correlations.

filename.out 

The log file for the CHARMM run, containing echoed commands, and various amounts of command output. The output print level may be increased or decreased in general, and procedures such as minimization and dynamics have printout frequency specifications. The values for temperature, energy pressure, etc. are output at that frequency.

References

1. ^ Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M (1983). "CHARMM: A program for macromolecular energy, minimization, and dynamics calculations". J Comp Chem 4: 187–217.
2. ^ MacKerell, A.D., Jr.; Brooks, B.; Brooks, C. L., III; Nilsson, L.; Roux, B.; Won, Y.; Karplus, M. (1998). "CHARMM: The Energy Function and Its Parameterization with an Overview of the Program". The Encyclopedia of Computational Chemistry 1. Ed. Schleyer, P.v.R.; et al. Chichester: John Wiley & Sons. 271-277. 
3. ^ Reiher, III WH (1985). "Theoretical studies of hydrogen bonding". PhD Thesis at Harvard University.
4. ^ MacKerell, Jr. AD, et al. (1998). "All-atom empirical potential for molecular modeling and dynamics studies of proteins". J Phys Chem B 102: 3586-3616.
5. ^ MacKerell, Jr. AD, Feig M, Brooks, III CL (2004). "Extending the treatment of backbone energetics in protein force fields: limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations". J Comput Chem 25: 1400-1415.
6. ^ Brooks CL, Chen J, Im W (2006). "Balancing solvation and intramolecular interactions: toward a consistent generalized born force field (CMAP opt. for GBSW)". J Am Chem Soc 128: 3728-3736.
7. ^ MacKerell, Jr. AD, Banavali N, Foloppe N (2001). "Development and current status of the CHARMM force field for nucleic acids". Biopolymers 56: 257-265.
8. ^ Lamoureux G, Roux B. (2003). Modeling induced polarization with classical Drude oscillators: Theory and molecular dynamics simulation algorithm. J Chem Phys 119(6):3025-3039.
9. ^ Lamoureux G, Harder E, Vorobyov IV, Roux B, MacKerell AD. (2006). A polarizable model of water for molecular dynamics simulations of biomolecules. Chem Phys Lett 418:245-9.
10. ^ Patel, S.; MacKerell, Jr. AD; Brooks III, Charles L (2004). "CHARMM fluctuating charge force field for proteins: I parameterization and application to bulk organic liquid simulations". J Comput Chem 25: 1-15.
11. ^ Patel, S.; MacKerell, Jr. AD; Brooks III, Charles L (2004). "CHARMM fluctuating charge force field for proteins: II protein/solvent properties from molecular dynamics simulations using a nonadditive electrostatic model". J Comput Chem 25: 1504-1514.
12. ^ Karplus M (2006). "Spinach on the ceiling: a theoretical chemist's return to biology". Annu Rev Biophys Biomol Struct 35: 1-47.