Enhancing the effectiveness of fingerprint-based virtual screening: use of turbo similarity searching and of fragment frequencies of occurrence

摘要

Binary fingerprints encoding the presence of 2D fragment substructures in molecules are extensively used for similarity-based virtual screening in the agrochemical and pharmaceutical industries. This paper describes two techniques for enhancing the effectiveness of screening: the use of a second-level search based on the nearest neighbours of the initial reference structure; and the use of weighted fingerprints encoding the frequency of occurrence, rather than just the mere presence, of substructures. Experiments using several databases for which both structural and bioactivity data are available demonstrate the effectiveness of these two approaches.