Estimation of the size of drug-like chemical space based on GDB-17 data

• Published in: Journal of computer-aided molecular design Vol. 27; no. 8; pp. 675 - 679
• Main Authors: Polishchuk, P. G., Madzhidov, T. I., Varnek, A.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.08.2013; Springer Nature B.V; Springer Verlag
• Subjects: Algorithms; Animal Anatomy; Atomic properties; CAD; Chemical compounds; Chemical Sciences; Cheminformatics; Chemistry; Chemistry and Materials Science; Computer aided design; Computer Applications in Chemistry; Databases, Pharmaceutical; Histology; Molecular Structure; Morphology; Pharmaceutical Preparations - chemistry; Physical Chemistry; Chemical space; Drug-like chemical space; Graphs enumeration
• ISSN: 0920-654X; 1573-4951
• DOI: 10.1007/s10822-013-9672-4

The goal of this paper is to estimate the number of realistic drug-like molecules which could ever be synthesized. Unlike previous studies based on exhaustive enumeration of molecular graphs or on combinatorial enumeration preselected fragments, we used results of constrained graphs enumeration by Reymond to establish a correlation between the number of generated structures ( M ) and the number of heavy atoms ( N ): log M  = 0.584 ×  N  × log N  + 0.356. The number of atoms limiting drug-like chemical space of molecules which follow Lipinsky’s rules ( N  = 36) has been obtained from the analysis of the PubChem database. This results in M  ≈ 10 33 which is in between the numbers estimated by Ertl (10 23 ) and by Bohacek (10 60 ).