Maximizing the Performance of Similarity-Based Virtual Screening Methods by Generating Synergy from the Integration of 2D and 3D Approaches
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 usi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/14/7747 |
| _version_ | 1797446501158354944 |
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| author | Ningning Fan Steffen Hirte Johannes Kirchmair |
| author_facet | Ningning Fan Steffen Hirte Johannes Kirchmair |
| author_sort | Ningning Fan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T13:42:17Z |
| format | Article |
| id | doaj.art-663037dd569d4b5b87c4943ae529e7ee |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T13:42:17Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-663037dd569d4b5b87c4943ae529e7ee2023-11-30T21:05:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012314774710.3390/ijms23147747Maximizing the Performance of Similarity-Based Virtual Screening Methods by Generating Synergy from the Integration of 2D and 3D ApproachesNingning Fan0Steffen Hirte1Johannes Kirchmair2Center for Bioinformatics (ZBH), Department of Informatics, Faculty of Mathematics, Informatics and Natural Sciences, Universität Hamburg, 20146 Hamburg, GermanyDivision of Pharmaceutical Chemistry, Department of Pharmaceutical Sciences, Faculty of Life Sciences, University of Vienna, 1090 Vienna, AustriaCenter for Bioinformatics (ZBH), Department of Informatics, Faculty of Mathematics, Informatics and Natural Sciences, Universität Hamburg, 20146 Hamburg, GermanyMethods 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.https://www.mdpi.com/1422-0067/23/14/7747virtual screeningvirtual screening strategiesshape-based virtual screeningsimilarity-based virtual screeningmolecular fingerprintsbenchmarking |
| spellingShingle | Ningning Fan Steffen Hirte Johannes Kirchmair Maximizing the Performance of Similarity-Based Virtual Screening Methods by Generating Synergy from the Integration of 2D and 3D Approaches International Journal of Molecular Sciences virtual screening virtual screening strategies shape-based virtual screening similarity-based virtual screening molecular fingerprints benchmarking |
| title | Maximizing the Performance of Similarity-Based Virtual Screening Methods by Generating Synergy from the Integration of 2D and 3D Approaches |
| title_full | Maximizing the Performance of Similarity-Based Virtual Screening Methods by Generating Synergy from the Integration of 2D and 3D Approaches |
| title_fullStr | Maximizing the Performance of Similarity-Based Virtual Screening Methods by Generating Synergy from the Integration of 2D and 3D Approaches |
| title_full_unstemmed | Maximizing the Performance of Similarity-Based Virtual Screening Methods by Generating Synergy from the Integration of 2D and 3D Approaches |
| title_short | Maximizing the Performance of Similarity-Based Virtual Screening Methods by Generating Synergy from the Integration of 2D and 3D Approaches |
| title_sort | maximizing the performance of similarity based virtual screening methods by generating synergy from the integration of 2d and 3d approaches |
| topic | virtual screening virtual screening strategies shape-based virtual screening similarity-based virtual screening molecular fingerprints benchmarking |
| url | https://www.mdpi.com/1422-0067/23/14/7747 |
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