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.cite journal | author = Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M | title=CHARMM: A program for macromolecular energy, minimization, and dynamics calculations | journal=J Comp Chem | volume=4 | pages=187–217 | year=1983 | doi=10.1002/jcc.540040211] [cite encyclopedia | last=MacKerell | first=A.D., Jr. | coauthors=Brooks, B.; Brooks, C. L., III; Nilsson, L.; Roux, B.; Won, Y.; Karplus, M. | title=CHARMM: The Energy Function and Its Parameterization with an Overview of the Program | encyclopedia=The Encyclopedia of Computational Chemistry | volume=1 | pages=271-277 | editor=Schleyer, P.v.R.; et al | publisher=John Wiley & Sons | location=Chichester | year=1998] 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.

CHARMM force fields

The CHARMM force fields for proteins include united-atom (sometimes called "extended atom") CHARMM19cite journal | author=Reiher, III WH | title=Theoretical studies of hydrogen bonding | journal=PhD Thesis at Harvard University| year=1985] , all-atom CHARMM22cite journal | author=MacKerell, Jr. AD, "et al." | year=1998 | title=All-atom empirical potential for molecular modeling and dynamics studies of proteins | journal=J Phys Chem B | volume=102 | pages=3586–3616 | doi=10.1021/jp973084f] and its dihedral potential corrected variant CHARMM22/CMAP.cite journal | author=MacKerell, Jr. AD, Feig M, Brooks, III CL | year=2004 | title=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 | journal=J Comput Chem | volume=25 | pages=1400–1415 | doi=10.1002/jcc.20065] 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.cite journal | author=Brooks CL, Chen J, Im W | year=2006 | title=Balancing solvation and intramolecular interactions: toward a consistent generalized born force field (CMAP opt. for GBSW) | journal=J Am Chem Soc | volume=128 | pages=3728–3736 | doi=10.1021/ja058206t]

For DNA, RNA, and lipids, CHARMM27cite journal | author=MacKerell, Jr. AD, Banavali N, Foloppe N | year=2001 | title=Development and current status of the CHARMM force field for nucleic acids | journal=Biopolymers | volume=56 | pages=257–265 | doi=10.1002/1097-0282(2000)56:4<257::AID-BIP10029>3.0.CO;2-W] 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. [http://www.pharmacy.umaryland.edu/faculty/amackere/force_fields.htm 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 fluctuating charge (FQ) model, also known as Charge Equilibration (CHEQ). cite journal | author=Patel, S.; MacKerell, Jr. AD; Brooks III, Charles L | year=2004 | title=CHARMM fluctuating charge force field for proteins: I parameterization and application to bulk organic liquid simulations | journal=J Comput Chem | volume=25 | pages=1–15 | doi=10.1002/jcc.10355] cite journal | author=Patel, S.; MacKerell, Jr. AD; Brooks III, Charles L | year=2004 | title=CHARMM fluctuating charge force field for proteins: II protein/solvent properties from molecular dynamics simulations using a nonadditive electrostatic model | journal=J Comput Chem | volume=25 | pages=1504–1514 | doi=10.1002/jcc.20077] The other is based on the Drude shell or dispersion oscillator model. 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.] 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.]

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 [http://www.charmm.org/package/changelogs/c34log.shtml 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 University of Michigan 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."cite journal | author=Karplus M | year=2006 | title=Spinach on the ceiling: a theoretical chemist's return to biology | journal=Annu Rev Biophys Biomol Struct | volume=35 | pages=1–47 | doi=10.1146/annurev.biophys.33.110502.133350] CHARMM has continued to grow and the latest release of the executable program was made in February 2008 as CHARMM34b2.

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.

CHARMM and Volunteer Computing

Docking@Home, hosted by University of Delaware, one of the projects which use a opensource platform for the distributed computing, BOINC, adopts CHARMM to analyze the atomic details of protein-ligand interactions in terms of Molecular Dynamics (MD) simulations and minimizations.

References

External links

* [http://www.accelrys.com/ Accelrys website]
* [http://www.charmm.org/ CHARMM website] with [http://www.charmm.org/document/Charmm/chmdoc.shtml documentation] and helpful [http://165.112.184.13//ubbthreads/ubbthreads.php?Cat= discussion forums]
* [http://www.ch.embnet.org/MD_tutorial/ CHARMM tutorial]
* [http://www.pharmacy.umaryland.edu/faculty/amackere/ MacKerell] website including a Package of [http://www.pharmacy.umaryland.edu/faculty/amackere/force_fields.htm force field parameters for CHARMM]
* [http://www.scripps.edu/brooks/ C.Brooks website]
* [http://yuri.harvard.edu/ CHARMM page at Harvard]
* [http://thallium.bsd.uchicago.edu/RouxLab/index.html Roux website]
* [http://www.lobos.nih.gov/cbs/index.php Bernard R. Brooks Group Website]
* [http://sirius.sdsc.edu Sirius] - visualization of CHARMM trajectories
* [http://docking.cis.udel.edu/ Docking@Home]