Editing Molecular dynamics (section)

=== Coarse-graining and reduced representations ===

At the other end of the detail scale are [[Coarse-grained modeling|coarse-grained]] and lattice models. Instead of explicitly representing every atom of the system, one uses "pseudo-atoms" to represent groups of atoms. MD simulations on very large systems may require such large computer resources that they cannot easily be studied by traditional all-atom methods. Similarly, simulations of processes on long timescales (beyond about 1 microsecond) are prohibitively expensive, because they require so many time steps. In these cases, one can sometimes tackle the problem by using reduced representations, which are also called [[Coarse-grained modeling|coarse-grained models]].<ref name=":0">{{cite journal | vauthors = Kmiecik S, Gront D, Kolinski M, Wieteska L, Dawid AE, Kolinski A | title = Coarse-Grained Protein Models and Their Applications | journal = Chemical Reviews | volume = 116 | issue = 14 | pages = 7898–7936 | date = July 2016 | pmid = 27333362 | doi = 10.1021/acs.chemrev.6b00163 | doi-access = free }}</ref>

Examples for coarse graining (CG) methods are discontinuous molecular dynamics (CG-DMD)<ref>{{cite journal | vauthors = Voegler Smith A, Hall CK | title = alpha-helix formation: discontinuous molecular dynamics on an intermediate-resolution protein model | journal = Proteins | volume = 44 | issue = 3 | pages = 344–360 | date = August 2001 | pmid = 11455608 | doi = 10.1002/prot.1100 | s2cid = 21774752 }}</ref><ref>{{cite journal | vauthors = Ding F, Borreguero JM, Buldyrey SV, Stanley HE, Dokholyan NV | title = Mechanism for the alpha-helix to beta-hairpin transition | journal = Proteins | volume = 53 | issue = 2 | pages = 220–228 | date = November 2003 | pmid = 14517973 | doi = 10.1002/prot.10468 | s2cid = 17254380 }}</ref> and Go-models.<ref>{{cite journal | vauthors = Paci E, Vendruscolo M, Karplus M | title = Validity of Gō models: comparison with a solvent-shielded empirical energy decomposition | journal = Biophysical Journal | volume = 83 | issue = 6 | pages = 3032–3038 | date = December 2002 | pmid = 12496075 | pmc = 1302383 | doi = 10.1016/S0006-3495(02)75308-3 | bibcode = 2002BpJ....83.3032P }}</ref> Coarse-graining is done sometimes taking larger pseudo-atoms. Such united atom approximations have been used in MD simulations of biological membranes. Implementation of such approach on systems where electrical properties are of interest can be challenging owing to the difficulty of using a proper charge distribution on the pseudo-atoms.<ref>{{cite journal | vauthors = Chakrabarty A, Cagin T |title=Coarse grain modeling of polyimide copolymers |journal=Polymer |date=May 2010 |volume=51 |issue=12 |pages=2786–2794 |doi=10.1016/j.polymer.2010.03.060 }}</ref> The aliphatic tails of lipids are represented by a few pseudo-atoms by gathering 2 to 4 methylene groups into each pseudo-atom.

The parameterization of these very coarse-grained models must be done empirically, by matching the behavior of the model to appropriate experimental data or all-atom simulations. Ideally, these parameters should account for both [[enthalpy|enthalpic]] and [[entropy|entropic]] contributions to free energy in an implicit way.<ref>{{cite journal | vauthors = Foley TT, Shell MS, Noid WG | title = The impact of resolution upon entropy and information in coarse-grained models | journal = The Journal of Chemical Physics | volume = 143 | issue = 24 | pages = 243104 | date = December 2015 | pmid = 26723589 | doi = 10.1063/1.4929836 | bibcode = 2015JChPh.143x3104F }}</ref> When coarse-graining is done at higher levels, the accuracy of the dynamic description may be less reliable. But very coarse-grained models have been used successfully to examine a wide range of questions in structural biology, liquid crystal organization, and polymer glasses.

Examples of applications of coarse-graining:
* [[protein folding]] and [[protein structure prediction]] studies are often carried out using one, or a few, pseudo-atoms per amino acid;<ref name=":0" />
* [[liquid crystal]] phase transitions have been examined in confined geometries and/or during flow using the [[Gay-Berne potential]], which describes anisotropic species;
* [[Polymer]] glasses during deformation have been studied using simple harmonic or [[FENE]] springs to connect spheres described by the [[Lennard-Jones potential]];
* [[Supercoiling|DNA supercoiling]] has been investigated using 1–3 pseudo-atoms per basepair, and at even lower resolution;
* Packaging of [[DNA|double-helical DNA]] into [[bacteriophage]] has been investigated with models where one pseudo-atom represents one turn (about 10 basepairs) of the double helix;
* RNA structure in the [[ribosome]] and other large systems has been modeled with one pseudo-atom per nucleotide.

The simplest form of coarse-graining is the ''united atom'' (sometimes called ''extended atom'') and was used in most early MD simulations of proteins, lipids, and nucleic acids. For example, instead of treating all four atoms of a CH<sub>3</sub> methyl group explicitly (or all three atoms of CH<sub>2</sub> methylene group), one represents the whole group with one pseudo-atom. It must, of course, be properly parameterized so that its van der Waals interactions with other groups have the proper distance-dependence. Similar considerations apply to the bonds, angles, and torsions in which the pseudo-atom participates. In this kind of united atom representation, one typically eliminates all explicit hydrogen atoms except those that have the capability to participate in hydrogen bonds (''polar hydrogens''). An example of this is the [[CHARMM]] 19 force-field.

The polar hydrogens are usually retained in the model, because proper treatment of hydrogen bonds requires a reasonably accurate description of the directionality and the electrostatic interactions between the donor and acceptor groups. A hydroxyl group, for example, can be both a hydrogen bond donor, and a hydrogen bond acceptor, and it would be impossible to treat this with one OH pseudo-atom. About half the atoms in a protein or nucleic acid are non-polar hydrogens, so the use of united atoms can provide a substantial savings in computer time.