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Article

Prediction of Protein−Protein Interaction Inhibitors by Chemoinformatics and Machine Learning Methods

Supporting Info

Alexander Neugebauer,^† Rolf W. Hartmann,^† and Christian D. Klein*^‡

Pharmaceutical and Medicinal Chemistry, Saarland University, Saarbrcken, Germany, and Medicinal Chemistry, University of Heidelberg, Heidelberg, Germany

J. Med. Chem., 2007, 50 (19), pp 4665–4668

DOI: 10.1021/jm070533j

Publication Date (Web): August 17, 2007

†

Saarland University.

To whom correspondence should be addressed. Dr. C. Klein, Medicinal Chemistry, University of Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany. Phone: ++49-6221-545824. Fax: ++49-6221-546430. E-mail: c.klein@uni-heidelberg.de.

‡

University of Heidelberg.

Abstract

We describe a collection of structurally diverse inhibitors of protein−protein-interactions (PPIs). This collection is compared against the FDA drug database and a subset of the ZINC database by machine learning methods which rely on classical QSAR descriptors. We obtain a decision tree that contains three descriptors. Of particular importance is a constitutional descriptor related to molecular shape and size. Validation of the decision tree by various procedures indicates that it does not result from chance correlations and has predictive value. We conclude that constitutional descriptors may be valuable tools in the preselection of potential PPI inhibitors from compound databases.

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