Efficient Substructure Searching of Large Chemical Libraries: The ABCD Chemical Cartridge

• Published in: Journal of chemical information and modeling Vol. 51; no. 12; pp. 3113 - 3130
• Main Authors: Agrafiotis, Dimitris K, Lobanov, Victor S, Shemanarev, Maxim, Rassokhin, Dmitrii N, Izrailev, Sergei, Jaeger, Edward P, Alex, Simson, Farnum, Michael
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 27.12.2011
• Subjects: Algorithms; Applied sciences; Atoms & subatomic particles; Biological and medical sciences; Chemical Information; Computer science; control theory; systems; Databases, Factual; Drug Discovery - economics; Exact sciences and technology; General pharmacology; Informatics - economics; Informatics - methods; Information management; Information retrieval. Graph; Information systems. Data bases; Medical sciences; Memory organisation. Data processing; Molecules; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; R&D; Research & development; Small Molecule Libraries - chemistry; Software; Theoretical computing; Time Factors; Capability index; Isomorphic graph; Acceptance; Database query; Relational database; Algorithmics; Very large databases; Experimental study; SQL; Screening; File structure; Pattern classification; Management information systems; Database; Problem solving; Cost estimation; Pharmaceutical industry; Oracle; Chemical system; User need; Indexing
• ISSN: 1549-9596; 1549-960X
• DOI: 10.1021/ci200413e

Efficient substructure searching is a key requirement for any chemical information management system. In this paper, we describe the substructure search capabilities of ABCD, an integrated drug discovery informatics platform developed at Johnson & Johnson Pharmaceutical Research & Development, L.L.C. The solution consists of several algorithmic components: 1) a pattern mapping algorithm for solving the subgraph isomorphism problem, 2) an indexing scheme that enables very fast substructure searches on large structure files, 3) the incorporation of that indexing scheme into an Oracle cartridge to enable querying large relational databases through SQL, and 4) a cost estimation scheme that allows the Oracle cost-based optimizer to generate a good execution plan when a substructure search is combined with additional constraints in a single SQL query. The algorithm was tested on a public database comprising nearly 1 million molecules using 4,629 substructure queries, the vast majority of which were submitted by discovery scientists over the last 2.5 years of user acceptance testing of ABCD. 80.7% of these queries were completed in less than a second and 96.8% in less than ten seconds on a single CPU, while on eight processing cores these numbers increased to 93.2% and 99.7%, respectively. The slower queries involved extremely generic patterns that returned the entire database as screening hits and required extensive atom-by-atom verification.