Enumeration of 166 Billion Organic Small Molecules in the Chemical Universe Database GDB-17

• Published in: Journal of chemical information and modeling Vol. 52; no. 11; pp. 2864 - 2875
• Main Authors: Ruddigkeit, Lars, van Deursen, Ruud, Blum, Lorenz C, Reymond, Jean-Louis
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 26-11-2012
• Subjects: Biological and medical sciences; Chemical bonds; Chemical, physic and infectious diseases; Computer Simulation; Databases, Chemical; Databases, Pharmaceutical; Drug Design; Drugs; General pharmacology; Medical sciences; Models, Chemical; Molecular Structure; Molecules; Occupational medicine; Organic chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Prescription Drugs - chemistry; Public health. Hygiene-occupational medicine; Stereoisomerism; Structure-Activity Relationship; Drug; Enumeration; Pharmaceutical technology; Organic molecule; Quaternary; Toxicity; Lead compound; Pressing; Chemical databasis; Covalent bond; Selectivity; Isomer
• ISSN: 1549-9596; 1549-960X
• DOI: 10.1021/ci300415d

Drug molecules consist of a few tens of atoms connected by covalent bonds. How many such molecules are possible in total and what is their structure? This question is of pressing interest in medicinal chemistry to help solve the problems of drug potency, selectivity, and toxicity and reduce attrition rates by pointing to new molecular series. To better define the unknown chemical space, we have enumerated 166.4 billion molecules of up to 17 atoms of C, N, O, S, and halogens forming the chemical universe database GDB-17, covering a size range containing many drugs and typical for lead compounds. GDB-17 contains millions of isomers of known drugs, including analogs with high shape similarity to the parent drug. Compared to known molecules in PubChem, GDB-17 molecules are much richer in nonaromatic heterocycles, quaternary centers, and stereoisomers, densely populate the third dimension in shape space, and represent many more scaffold types.