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. It contains millions of compounds which are readily accessible and available to researchers. It is a library used in the method of molecular docking. [2]
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 determining the precise size of this space. The assumptions [3] 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 to be the estimated size of the whole organic chemistry space, [4] which would be much larger if including the halogens and other elements. In addition to the drug-like space and lead-like space that are, in part, defined by the Lipinski's rule of five, the concept of known drug space (KDS), which is defined by the molecular descriptors of marketed drugs, has also been introduced. [5] [6] [7] KDS can be used to help predict the boundaries of chemical spaces for drug development by comparing the structure of the molecules that are undergoing design and synthesis to the molecular descriptor parameters that are defined by the KDS.
As of October 2024, 219 million molecules were assigned with a Chemical Abstracts Service (CAS) Registry Number. [8] ChEMBL Database version 33 record biological activities for 2,431,025 distinct molecules. [9] [10] 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).
Systematic exploration of chemical space is possible by creating in silico databases of virtual molecules, [11] which can be visualized by projecting multidimensional property space of molecules in lower dimensions. [12] [13] 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. Materials design and drug discovery both involve the exploration of chemical space.
A chemical database is a database specifically designed to store chemical information. This information is about chemical and crystal structures, spectra, reactions and syntheses, and thermophysical data.
Cheminformatics refers to the use of physical chemistry theory with computer and information science techniques—so called "in silico" techniques—in application to a range of descriptive and prescriptive problems in the field of chemistry, including in its applications to biology and related molecular fields. Such in silico techniques are used, for example, by pharmaceutical companies and in academic settings to aid and inform the process of drug discovery, for instance in the design of well-defined combinatorial libraries of synthetic compounds, or to assist in structure-based drug design. The methods can also be used in chemical and allied industries, and such fields as environmental science and pharmacology, where chemical processes are involved or studied.
Chemical Markup Language is an approach to managing molecular information using tools such as XML and Java. It was the first domain specific implementation based strictly on XML, first based on a DTD and later on an XML Schema, the most robust and widely used system for precise information management in many areas. It has been developed over more than a decade by Murray-Rust, Rzepa and others and has been tested in many areas and on a variety of machines.
Quantitative structure–activity relationship models are regression or classification models used in the chemical and biological sciences and engineering. Like other regression models, QSAR regression models relate a set of "predictor" variables (X) to the potency of the response variable (Y), while classification QSAR models relate the predictor variables to a categorical value of the response variable.
A molecule editor is a computer program for creating and modifying representations of chemical structures.
PubChem is a database of chemical molecules and their activities against biological assays. The system is maintained by the National Center for Biotechnology Information (NCBI), a component of the National Library of Medicine, which is part of the United States National Institutes of Health (NIH). PubChem can be accessed for free through a web user interface. Millions of compound structures and descriptive datasets can be freely downloaded via FTP. PubChem contains multiple substance descriptions and small molecules with fewer than 100 atoms and 1,000 bonds. More than 80 database vendors contribute to the growing PubChem database.
JOELib is computer software, a chemical expert system used mainly to interconvert chemical file formats. Because of its strong relationship to informatics, this program belongs more to the category cheminformatics than to molecular modelling. It is available for Windows, Unix and other operating systems supporting the programming language Java. It is free and open-source software distributed under the GNU General Public License (GPL) 2.0.
Molecule mining is the process of data mining, or extracting and discovering patterns, as applied to molecules. Since molecules may be represented by molecular graphs, this is strongly related to graph mining and structured data mining. The main problem is how to represent molecules while discriminating the data instances. One way to do this is chemical similarity metrics, which has a long tradition in the field of cheminformatics.
Substructure search (SSS) is a method to retrieve from a database only those chemicals matching a pattern of atoms and bonds which a user specifies. It is an application of graph theory, specifically subgraph matching in which the query is a hydrogen-depleted molecular graph. The mathematical foundations for the method were laid in the 1870s, when it was suggested that chemical structure drawings were equivalent to graphs with atoms as vertices and bonds as edges. SSS is now a standard part of cheminformatics and is widely used by pharmaceutical chemists in drug discovery.
The ZINC database is a curated collection of commercially available chemical compounds prepared especially for virtual screening. ZINC is used by investigators in pharmaceutical companies, biotechnology companies, and research universities.
ChemSpider is a freely accessible online database of chemicals owned by the Royal Society of Chemistry. It contains information on more than 100 million molecules from over 270 data sources, each of them receiving a unique identifier called ChemSpider Identifier.
Chemaxon is a cheminformatics and bioinformatics software development company, headquartered in Budapest with 250 employees. The company also has offices in Cambridge, San Diego, Basel and in Prague. and it has distributors in China, India, Japan, South Korea, Singapore, and Australia. Chemaxon was acquired by Certara on July 9th, 2024.
Chemical similarity refers to the similarity of chemical elements, molecules or chemical compounds with respect to either structural or functional qualities, i.e. the effect that the chemical compound has on reaction partners in inorganic or biological settings. Biological effects and thus also similarity of effects are usually quantified using the biological activity of a compound. In general terms, function can be related to the chemical activity of compounds.
ChEMBL or ChEMBLdb is a manually curated chemical database of bioactive molecules with drug inducing properties. It is maintained by the European Bioinformatics Institute (EBI), of the European Molecular Biology Laboratory (EMBL), based at the Wellcome Trust Genome Campus, Hinxton, UK.
Antony John Williams is a British chemist and expert in the fields of both nuclear magnetic resonance (NMR) spectroscopy and cheminformatics at the United States Environmental Protection Agency. He is the founder of the ChemSpider website that was purchased by the Royal Society of Chemistry in May 2009. He is a science blogger and an author.
Druggability is a term used in drug discovery to describe a biological target that is known to or is predicted to bind with high affinity to a drug. Furthermore, by definition, the binding of the drug to a druggable target must alter the function of the target with a therapeutic benefit to the patient. The concept of druggability is most often restricted to small molecules but also has been extended to include biologic medical products such as therapeutic monoclonal antibodies.
Matched molecular pair analysis (MMPA) is a method in cheminformatics that compares the properties of two molecules that differ only by a single chemical transformation, such as the substitution of a hydrogen atom by a chlorine one. Such pairs of compounds are known as matched molecular pairs (MMP). Because the structural difference between the two molecules is small, any experimentally observed change in a physical or biological property between the matched molecular pair can more easily be interpreted. The term was first coined by Kenny and Sadowski in the book Chemoinformatics in Drug Discovery.
The hierarchical editing language for macromolecules (HELM) is a method of describing complex biological molecules. It is a notation that is machine readable to render the composition and structure of peptides, proteins, oligonucleotides, and related small molecule linkers.
Building block is a term in chemistry which is used to describe a virtual molecular fragment or a real chemical compound the molecules of which possess reactive functional groups. Building blocks are used for bottom-up modular assembly of molecular architectures: nano-particles, metal-organic frameworks, organic molecular constructs, supra-molecular complexes. Using building blocks ensures strict control of what a final compound or a (supra)molecular construct will be.