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

TLDR

Drug molecules are small covalently bonded structures, and medicinal chemists seek to expand this space to improve potency, selectivity, and reduce toxicity. The study aims to determine the total number and structural characteristics of all possible small drug‑like molecules. The authors enumerated 166.4 billion molecules up to 17 atoms of C, N, O, S, and halogens to create the GDB‑17 database. GDB‑17 contains millions of drug isomers and many analogs with high shape similarity, and it is richer in nonaromatic heterocycles, quaternary centers, stereoisomers, and scaffold types than PubChem, densely populating three‑dimensional shape space.

Abstract

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.