Methods for Effective Virtual Screening and Scaffold-Hopping in Chemical Compounds

Nikil Wale and George Karypis
Computational Systems Biology (CSB), pp. 403-416, 2007
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Methods that can screen large databases to retrieve a structurally diverse set of
compounds with desirable bioactivity properties are critical in the drug discovery and
development process. This paper presents a set of such methods, which are designed to
find compounds that are structurally different to a certain query compound while retaining
its bioactivity properties (scaffold hops). These methods utilize various indirect ways
of measuring the similarity between the query and a compound that take into account
additional information beyond their structure-based similarities. Two sets of techniques
are presented that capture these indirect similarities using approaches based on automatic
relevance feedback and on analyzing the similarity network formed by the query and the
database compounds. Experimental evaluation shows that many of these methods
substantially outperform previously developed approaches both in terms of their ability to
identify structurally diverse active compounds as well as active compounds in general.
Research topics: AFGen | Bioinformatics | Cheminformatics | Information retrieval | Social networks