CHARMM
Encyclopedia
CHARMM is the name of a widely used set of force field
s for molecular dynamics
as well as the name for the molecular dynamics simulation and analysis package
associated with them. 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
.
s for proteins include: united-atom (sometimes called "extended atom") CHARMM19, all-atom CHARMM22 and its dihedral potential corrected variant CHARMM22/CMAP. 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. In 2006, a special version of CHARMM22/CMAP was reparametrized for consistent use with implicit solvent GBSW.
For DNA
, RNA
, and lipids, CHARMM27 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.
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". 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 known as 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.
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 University of Michigan
is very salient.
'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
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." CHARMM has continued to grow and the latest release of the executable program was made in August 2009 as CHARMM35b3.
charmm -i filename.inp -o 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.
, 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.
World Community Grid
, sponsored by IBM, runs a project called The Clean Energy Project which also uses CHARMM.
Force field (chemistry)
In the context of molecular modeling, a force field refers to the form and parameters of mathematical functions used to describe the potential energy of a system of particles . Force field functions and parameter sets are derived from both experimental work and high-level quantum mechanical...
s for molecular dynamics
Molecular dynamics
Molecular dynamics is a computer simulation of physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a period of time, giving a view of the motion of the atoms...
as well as the name for the molecular dynamics simulation and analysis package
Software package (installation)
In package management systems, which are commonly used with Linux-based operating systems, a package is a specific piece of software which the system can install and uninstall....
associated with them. The CHARMM Development Project involves a network of developers throughout the world working with Martin Karplus
Martin Karplus
Martin Karplus is an Austrian-born American theoretical chemist. He has been Theodore William Richards Professor of Chemistry at Harvard University since 1979...
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
Accelrys
Accelrys is a software company headquartered in the US, with representation in Europe and Japan. It provides software for chemical, materials and bioscience research for the pharmaceutical, biotechnology, consumer packaged goods, aerospace, energy and chemical industries.Accelrys started in 2001...
.
CHARMM force fields
The CHARMM force fieldForce field (chemistry)
In the context of molecular modeling, a force field refers to the form and parameters of mathematical functions used to describe the potential energy of a system of particles . Force field functions and parameter sets are derived from both experimental work and high-level quantum mechanical...
s for proteins include: united-atom (sometimes called "extended atom") CHARMM19, all-atom CHARMM22 and its dihedral potential corrected variant CHARMM22/CMAP. 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
Water model
In computational chemistry, classical water models are used for the simulation of water clusters, liquid water, and aqueous solutions with explicit solvent. These models use the approximations of molecular mechanics...
. Nevertheless, it is frequently used with implicit solvents. In 2006, a special version of CHARMM22/CMAP was reparametrized for consistent use with implicit solvent GBSW.
For DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
, RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
, and lipids, CHARMM27 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.
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". 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 known as Charge Equilibration (CHEQ). The other is based on the Drude
Drude particle
Drude particles are model oscillators used to simulate the effects of electronic polarizability in the context of a classical molecular mechanics force field. It is based on the Drude model of mobile electrons...
shell or dispersion oscillator model.
Parameters for all of these force fields may be downloaded from the Mackerell website for free.
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
Free energy perturbation
Free energy perturbation theory is a method based on statistical mechanics that is used in computational chemistry for computing free energy differences from molecular dynamics or Metropolis Monte Carlo simulations. The FEP method was introduced by R. W. Zwanzig in 1954...
(FEP), quasi-harmonic entropy estimation, correlation analysis and combined quantum, and molecular mechanics
Molecular mechanics
Molecular mechanics uses Newtonian mechanics to model molecular systems. The potential energy of all systems in molecular mechanics is calculated using force fields...
(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 University of Michigan
University of Michigan
The University of Michigan is a public research university located in Ann Arbor, Michigan in the United States. It is the state's oldest university and the flagship campus of 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 KarplusMartin Karplus
Martin Karplus is an Austrian-born American theoretical chemist. He has been Theodore William Richards Professor of Chemistry at Harvard University since 1979...
'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 WarshelArieh WarshelArieh Warshel is a Distinguished Professor of Chemistry and Biochemistry at the University of Southern California. He is known for his work on computational biochemistry and biophysics, and, in particular, for having pioneered computer simulations of the function of biological systems, and for...
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 LevittMichael LevittProfessor Michael Levitt FRS is a British biophysicist. He has been Professor of Structural biology, Stanford University, California, since 1987 working in computational biology and bioinformatics....
'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." CHARMM has continued to grow and the latest release of the executable program was made in August 2009 as CHARMM35b3.
Running CHARMM Under Unix/Linux
The general syntax for using the program is:charmm -i filename.inp -o 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
Force field (chemistry)
In the context of molecular modeling, a force field refers to the form and parameters of mathematical functions used to describe the potential energy of a system of particles . Force field functions and parameter sets are derived from both experimental work and high-level quantum mechanical...
(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@HomeDocking@Home
Docking@Home is a distributed computing project hosted by the University of Delaware and running on the Berkeley Open Infrastructure for Network Computing software platform. It models protein-ligand docking using the CHARMM program. The ultimate aim is the development of new pharmaceutical...
, hosted by University of Delaware, one of the projects which use a opensource platform for the distributed computing
Distributed computing
Distributed computing is a field of computer science that studies distributed systems. A distributed system consists of multiple autonomous computers that communicate through a computer network. The computers interact with each other in order to achieve a common goal...
, BOINC, adopts CHARMM to analyze the atomic details of protein-ligand interactions in terms of Molecular Dynamics
Molecular dynamics
Molecular dynamics is a computer simulation of physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a period of time, giving a view of the motion of the atoms...
(MD) simulations and minimizations.
World Community Grid
World Community Grid
World Community Grid is an effort to create the world's largest public computing grid to tackle scientific research projects that benefit humanity...
, sponsored by IBM, runs a project called The Clean Energy Project which also uses CHARMM.
See also
External links
- Accelrys website
- CHARMM website with documentation and helpful discussion forums
- CHARMM tutorial
- MacKerell website including a Package of force field parameters for CHARMM
- C.Brooks website
- CHARMM page at Harvard
- Roux website
- Bernard R. Brooks Group Website
- Docking@Home
- CHARMM-GUI project
- CHARMMing (CHARMM Interface and Graphics)
- CHARMM Tutorial