Chemical space

View of PubChem chemical space; a projection of the 42-dimensional MQN-property space of PubChem (with 5 virtually created libraries of compounds) using PCA. Color coding is according to fraction (blue 0, red 1) of ring atoms in molecules.[1]

Chemical space is a concept in cheminformatics referring to the property space spanned by all possible molecules and chemical compounds adhering to a given set of construction principles and boundary conditions.

Theoretical Chemical Spaces

A chemical space often referred to in cheminformatics is that of potential pharmacologically active molecules. Its size is estimated to be in the order of 1060 molecules. There are no rigorous methods for determine the precise size of this space. The assumptions [2] used for estimating the number of potential pharmacologically active molecules, however, use the Lipinski rules, in particular the molecular weight limit of 500. The estimate also restricts the chemical elements used to be Carbon, Hydrogen, Oxygen, Nitrogen and Sulfur. It further makes the assumption of a maximum of 30 atoms to stay below 500 Daltons, allows for branching and a maximum of 4 rings and arrives at an estimate of 1063. This number is often misquoted in subsequent publications [3] to be the estimated size of the whole organic chemistry space, which, however, will be much larger through considering the potential introduction of the halogens and other elements.

Concrete Chemical Spaces

As of July 2009, there were 49,037,297 organic and inorganic substances registered with the Chemical Abstracts Service, indicating that they have been reported in the scientific literature.[4] Chemical libraries used for laboratory-based screening for compounds with desired properties are examples for real-world chemical libraries of small size (a few hundred to hundreds of thousands of molecules).

Generation of Chemical Spaces

Systematic exploration of chemical space is possible by creating in silico databases of virtual molecules,[5] which can be visualized by projecting multidimensional property space of molecules in lower dimensions.[6][7] Generation of chemical spaces may involve creating stoichiometric combinations of electrons and atomic nuclei to yield all possible topology isomers for the given construction principles. In Cheminformatics, software programs called Structure Generators are used to generate the set of all chemical structure adhering to given boundary conditions. Constitutional Isomer Generators, for example, can generate all possible constitutional isomers of a given molecular gross formula.

In the real world, Chemical reactions allow us to move in chemical space. The mapping between chemical space and molecular properties is often not unique, meaning that there can be very different molecules exhibiting very similar properties. Material design and drug discovery both involve the exploration of chemical space.

See also

References

  1. ↑ Reymond, J.-L.; Awale, M. (2012). "Exploring chemical space for drug discovery using the chemical universe database.". ACS Chem. Neurosci. 3 (9): 649–657. doi:10.1021/cn3000422. PMID 23019491.
  2. ↑ Bohacek, R .S.; C. McMartin; W. C. Guida (1999). "The art and practice of structure‐based drug design: A molecular modeling perspective". Medicinal Research Reviews (1): 3–50. doi:10.1002/(SICI)1098-1128(199601)16:1<3::AID-MED1>3.0.CO;2-6.
  3. ↑ Kirkpatrick, P.; C. Ellis (2004). "Chemical space". Nature. 432 (432): 823–865. Bibcode:2004Natur.432..823K. doi:10.1038/432823a.
  4. ↑ http://www.cas.org/cgi-bin/cas/regreport.pl
  5. ↑ L. Ruddigkeit; R. van Deursen; L. C. Blum; J.-L. Reymond (2012). "Enumeration of 166 Billion Organic Small Molecules in the Chemical Universe Database GDB-17". J. Chem. Inf. Model. 52 (11): 2864–2875. doi:10.1021/ci300415d. PMID 23088335.
  6. ↑ M. Awale; R. van Deursen; J. L. Reymond (2013). "MQN-Mapplet: Visualization of Chemical Space with Interactive Maps of DrugBank, ChEMBL, PubChem, GDB-11, and GDB-13". J. Chem. Inf. Model. 53 (2): 509–18. doi:10.1021/ci300513m. PMID 23297797.
  7. ↑ L. Ruddigkeit; L. C. Blum; J.-L. Reymond (2013). "Visualization and Virtual Screening of the Chemical Universe Database GDB-17". J. Chem. Inf. Model. 53 (1): 56–65. doi:10.1021/ci300535x. PMID 23259841.


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