Editing CHARMM

{{Infobox software
|name                   = CHARMM
|logo                   = 
|screenshot             = 
|caption                = 
|developer              = [[Martin Karplus]], [[Accelrys]]
|released               = {{Start date and age|1983}}
|latest release version = c47b1
|latest release date    = {{Start date and age|2022|df=yes}}<ref name="versions">{{cite web 
  |url=https://www.academiccharmm.org/program/versions
  |title=Versions - CHARMM
  |website=CHARMM (Chemistry at HARvard Macromolecular Mechanics) 
  |publisher=Harvard University 
  |access-date=2021-03-29
}}</ref>
|latest preview version = c48a1
|latest preview date    = {{Start date and age|2022|df=yes}}<ref name="versions"/>
|programming language   = [[FORTRAN]] 77-95, [[CUDA]]
|operating system       = [[Unix-like]]: [[Linux]], [[macOS]], [[IBM AIX|AIX]], [[iOS]]<ref name="OS+platforms">{{cite web 
  |url=https://www.academiccharmm.org/documentation/installation#Documentation
  |title=Installation 
  |author=<!--Staff writer(s); no by-line.--> 
  |date=2016 
  |website=CHARMM (Chemistry at HARvard Macromolecular Mechanics) 
  |publisher=Harvard University 
  |access-date=2021-03-29
}}</ref>
|platform               = [[x86]], [[ARM architecture|ARM]], [[Nvidia]] [[Graphics processing unit|GPU]]; [[Cray]] [[Cray XT4|XT4]], [[Cray XT5|XT5]]<ref name="OS+platforms" />
|size                   = 
|language               = English
|genre                  = [[Molecular dynamics]]
|license                = [[Proprietary software|Proprietary]]
|website                = {{URL|https://www.academiccharmm.org/}}
}}

'''Chemistry at Harvard Macromolecular Mechanics''' ('''CHARMM''') is the name of a widely used set of [[force field (chemistry)|force field]]s for [[molecular dynamics]], and the name for the molecular dynamics simulation and analysis computer [[software]] package associated with them.<ref name=Brooks1983>{{cite journal |vauthors=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. Comput. Chem. |volume=4 |issue= 2 |pages=187–217 |year=1983 |doi=10.1002/jcc.540040211|s2cid=91559650 }}</ref><ref>{{cite encyclopedia |last=MacKerell |first=A.D. Jr. |last2=Brooks |first2=B. |last3=Brooks |first3=C. L. III |last4=Nilsson |first4=L. |last5=Roux |first5=B. |last6=Won |first6= Y.|last7=Karplus |first7=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. |publisher=John Wiley & Sons |location=Chichester |year=1998|display-editors=etal}}</ref><ref>{{cite journal |vauthors=Brooks BR, Brooks CL 3rd, Mackerell AD Jr, Nilsson L, Petrella RJ, Roux B, Won Y, Archontis G, Bartels C, Boresch S, Caflisch A, Caves L, Cui Q, Dinner AR, Feig M, Fischer S, Gao J, Hodoscek M, Im W, Kuczera K, Lazaridis T, Ma J, Ovchinnikov V, Paci E, Pastor RW, Post CB, Pu JZ, Schaefer M, Tidor B, Venable RM, Woodcock HL, Wu X, Yang W, York DM, Karplus M |title=CHARMM: The biomolecular simulation program |journal=Journal of Computational Chemistry |date=29 July 2009 |volume=30 |issue=10 |pages=1545–1614 |doi=10.1002/jcc.21287 |pmid=19444816 |pmc=2810661}}</ref> The CHARMM Development Project involves a worldwide network of developers 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.

== Force fields ==
The CHARMM [[force field (chemistry)|force field]]s for proteins include: united-atom (sometimes termed ''extended atom'') CHARMM19,<ref name=Reiher1985>{{cite thesis |author=Reiher, III WH |title=Theoretical studies of hydrogen bonding |publisher=Harvard University| year=1985}}</ref> all-atom CHARMM22<ref name=MacKerell1998>{{cite journal |author=MacKerell AD Jr| year=1998 |title=All-atom empirical potential for molecular modeling and dynamics studies of proteins |journal=J Phys Chem B |volume=102 |issue=18 |pages=3586–3616 |doi=10.1021/jp973084f|display-authors=etal |pmid=24889800}}</ref> and its dihedral potential corrected variant CHARMM22/CMAP, as well as later versions CHARMM27 and CHARMM36 and various modifications such as CHARMM36m and CHARMM36IDPSFF.<ref name=MacKerell2004a>{{cite journal |vauthors=MacKerell AD Jr, 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 |pmid=15185334 |issue=11|s2cid=11076418 }}</ref> 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 often used with [[implicit solvent]]s. In 2006, a special version of CHARMM22/CMAP was reparametrized for consistent use with implicit solvent GBSW.<ref name=Brooks2006>{{cite journal |vauthors=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/ja057216r |pmid=16536547 |issue=11 |pmc=2596729}}</ref>

The CHARMM22 force field has the following potential energy function:<ref name=MacKerell1998 /><ref>{{Cite journal |last1=Vanommeslaeghe |first1=K. |last2=MacKerell |first2=A. D. |date=May 2015 |title=CHARMM additive and polarizable force fields for biophysics and computer-aided drug design |journal=Biochimica et Biophysica Acta (BBA) - General Subjects |volume=1850 |issue=5 |pages=861–871 |doi=10.1016/j.bbagen.2014.08.004 |issn=0006-3002 |pmc=4334745 |pmid=25149274}}</ref>

<math>\begin{align}V=&\sum_{bonds}k_b(b-b_0)^2+\sum_{angles}k_{\theta}(\theta-\theta_0)^2+\sum_{dihedrals}k_\phi[1+\cos(n\phi-\delta)]\\
&+\sum_{impropers}k_\omega(\omega-\omega_0)^2+\sum_{Urey-Bradley}k_u(u-u_0)^2\\
&+\sum_{nonbonded}\left(\epsilon_{ij}\left[\left(\frac{R_{min_{ij}}}{r_{ij}}\right)^{12}-2\left(\frac{R_{min_{ij}}}{r_{ij}}\right)^6\right]+\frac{q_i q_j}{\epsilon_r r_{ij}}\right)\end{align}</math>

The bond, angle, dihedral, and nonbonded terms are similar to those found in other force fields such as [[AMBER#Functional_form|AMBER]]. The CHARMM force field also includes an improper term accounting for out-of-plane bending (which applies to any set of four atoms that are not successively bonded), where <math>k_\omega</math> is the force constant and <math>\omega-\omega_0</math> is the out-of-plane angle. The Urey-Bradley term is a cross-term that accounts for 1,3 nonbonded interactions not accounted for by the bond and angle terms; <math>k_u</math> is the force constant and <math>u</math> is the distance between the 1,3 atoms.

For [[DNA]], [[RNA]], and [[lipid]]s, CHARMM27<ref name=MacKerell2001>{{cite journal |vauthors=MacKerell AD Jr, 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 |pmid=11754339 |issue=4|s2cid=19502363 }}</ref> is used. Some force fields may be combined, for example CHARMM22 and CHARMM27 for the simulation of protein-DNA binding. Also, 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.

In 2009, a general force field for drug-like molecules (CGenFF) was introduced. It "covers a wide range of chemical groups present in biomolecules and drug-like molecules, including a large number of heterocyclic scaffolds".<ref name=Vanommeslaeghe>{{cite journal |vauthors=Vanommeslaeghe K, Hatcher E, Acharya C, Kundu S, Zhong S, Shim J, Darian E, Guvench O, Lopes P, Vorobyov I, ((Mackerell AD Jr)) |year=2009 |title=CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields |journal=J Comput Chem |volume= 31| pages= 671–90| doi=10.1002/jcc.21367 |pmc=2888302 |pmid=19575467 |issue=4}}</ref> The general force field is designed to cover any combination of chemical groups. This 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).<ref name=Patel2004a>{{cite journal |vauthors=Patel S, Brooks CL 3rd |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 |pmid=14634989 |issue=1|s2cid=39320318 }}</ref><ref name=Patel2004b>{{cite journal |vauthors=Patel S, Mackerell AD Jr, Brooks CL 3rd |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 |pmid=15224394 |issue=12|s2cid=16741310 |doi-access=free }}</ref> The other is based on the [[Drude particle|Drude]] shell or dispersion oscillator model.<ref name="Lamoureux">{{cite journal |vauthors=Lamoureux G, Roux B |year=2003 |title=Modeling induced polarization with classical Drude oscillators: Theory and molecular dynamics simulation algorithm |journal=J Chem Phys |volume=119 |issue=6 |pages=3025–3039 |doi=10.1063/1.1589749|bibcode= 2003JChPh.119.3025L|doi-access=free }}</ref><ref name="Lamoureux3">{{cite journal |vauthors=Lamoureux G, Harder E, Vorobyov IV, Roux B, MacKerell AD |year=2006 |title=A polarizable model of water for molecular dynamics simulations of biomolecules |journal=Chem Phys Lett |volume=418 |issue=1–3 |pages=245–249 |doi=10.1016/j.cplett.2005.10.135|bibcode= 2006CPL...418..245L}}</ref>

Parameters for all of these force fields may be downloaded from the Mackerell website for free.<ref>[http://mackerell.umaryland.edu/CHARMM_ff_params.html Mackerell website]</ref>

== 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 [https://web.archive.org/web/20070907000754/http://www.charmm.org/package/changelogs/c34log.shtml 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 (biophysicist)|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 seemed inappropriate. 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.''"<ref name=Karplus2006>{{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 |issue=1 |pages=1–47 |doi=10.1146/annurev.biophys.33.110502.133350 |pmid=16689626|doi-access= }}</ref> CHARMM has continued to grow and the latest release of the executable program was made in 2015 as CHARMM40b2.

== Running CHARMM under Unix-Linux ==
The general syntax for using the program is:

<code>charmm -i filename.inp -o filename.out</code>

* <code>charmm</code> – The name of the program (or script which runs the program) on the computer system being used.
* <code>filename.inp</code> – A text file which contains the CHARMM commands. It starts by loading the molecular topologies (top) and [[Force field (chemistry)|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.
* <code>filename.out</code> – 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.

== Volunteer computing ==
[[Docking@Home]], hosted by University of Delaware, one of the projects which use an [[open-source software|open-source]] platform for the [[distributed computing]], [[BOINC]], used CHARMM to analyze the atomic details of protein-ligand interactions in terms of [[molecular dynamics]] (MD) simulations and minimizations.

[[World Community Grid]], sponsored by IBM, ran a project named The Clean Energy Project<ref>[http://www.worldcommunitygrid.org/projects_showcase/cep1/viewCep1Main.do The Clean Energy Project]</ref> which also used CHARMM in its first phase, which has been completed.

==See also==
{{columns-list|colwidth=30em|
* [[AMBER]]
* [[Ascalaph Designer]]
* [[GROMACS]]
* [[NAMD]]
* [[Comparison of force field implementations]]
* [[Comparison of software for molecular mechanics modeling]]
* [[MacroModel]]
* [[MDynaMix]]
* [[OPLS]]
* [[X-PLOR]]
* [[Yasara]]
}}

==References==
{{Reflist|2}}

== External links ==
* {{Official website|www.academiccharmm.org}}, with [https://www.academiccharmm.org/documentation documentation] and helpful [https://www.charmm.org//ubbthreads/ubbthreads.php?Cat= discussion forums]
* {{Official website|http://accelrys.com/products/collaborative-science/biovia-discovery-studio/simulations.html}}, BIOVIA
* [http://www.ch.embnet.org/MD_tutorial/ CHARMM tutorial]; {{Webarchive|url=https://web.archive.org/web/20101005042034/http://www.ch.embnet.org/MD_tutorial/ |date=2010-10-05 }}
* [http://www.pharmacy.umaryland.edu/faculty/amackere/ MacKerell] website, hosts package of force field parameters for CHARMM
* [https://web.archive.org/web/20121017144252/http://brooks.chem.lsa.umich.edu/ C.Brooks website]
* [http://yuri.harvard.edu/ CHARMM page at Harvard]
* [http://thallium.bsd.uchicago.edu/RouxLab/ Roux website]; {{Webarchive|url=https://web.archive.org/web/20061012004711/http://thallium.bsd.uchicago.edu/RouxLab/ |date=2006-10-12 }}
* [http://www.lobos.nih.gov/cbs/ Bernard R. Brooks Group website]
* [http://docking.cis.udel.edu/ Docking@Home]
* [http://www.charmm-gui.org/ CHARMM-GUI project]
* [http://www.charmming.org/ CHARMMing (CHARMM Interface and Graphics)]; {{Webarchive|url=https://web.archive.org/web/20080820003831/http://www.charmming.org/ |date=2008-08-20 }}
* {{usurped|1=[https://web.archive.org/web/20080515090156/http://www.charmmtutorial.org/ CHARMM Tutorial]}}

{{Chemistry software}}

[[Category:Force fields (chemistry)]]
[[Category:Fortran software]]
[[Category:Harvard University]]
[[Category:Molecular dynamics software]]