Titel
Maximizing the Performance of Similarity-Based Virtual Screening Methods by Generating Synergy from the Integration of 2D and 3D Approaches
Autor*in
Ningning Fan
Center for Bioinformatics (ZBH), Department of Informatics, Faculty of Mathematics, Informatics and Natural Sciences, Universität Hamburg
Abstract
Methods for the pairwise comparison of 2D and 3D molecular structures are established approaches in virtual screening. In this work, we explored three strategies for maximizing the virtual screening performance of these methods: (i) the merging of hit lists obtained from multi-compound screening using a single screening method, (ii) the merging of the hit lists obtained from 2D and 3D screening by parallel selection, and (iii) the combination of both of these strategies in an integrated approach. We found that any of these strategies led to a boost in virtual screening performance, with the clearest advantages observed for the integrated approach. On test sets for virtual screening, covering 50 pharmaceutically relevant proteins, the integrated approach, using sets of five query molecules, yielded, on average, an area under the receiver operating characteristic curve (AUC) of 0.84, an early enrichment among the top 1% of ranked compounds (EF1%) of 53.82 and a scaffold recovery rate among the top 1% of ranked compounds (SRR1%) of 0.50. In comparison, the 2D and 3D methods on their own (when using a single query molecule) yielded AUC values of 0.68 and 0.54, EF1% values of 19.96 and 17.52, and SRR1% values of 0.20 and 0.17, respectively. In conclusion, based on these results, the integration of 2D and 3D methods, via a (balanced) parallel selection strategy, is recommended, and, in particular, when combined with multi-query screening.
Stichwort
virtual screeningvirtual screening strategiesshape-based virtual screeningsimilarity-based virtual screeningmolecular fingerprintsbenchmarking
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
Erschienen in
Titel
International Journal of Molecular Sciences
Band
23
Ausgabe
14
ISSN
1422-0067
Erscheinungsdatum
2022
Publication
MDPI AG
Erscheinungsdatum
2022
Zugänglichkeit
Rechte
Rechteangabe
© 2022 by the authors
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