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Assessment of the fragment docking program SEED


Goossens, Kenneth; Wroblowski, Berthold; Langini, Cassiano; van Vlijmen, Herman; Caflisch, Amedeo; De Winter, Hans (2020). Assessment of the fragment docking program SEED. Journal of Chemical Information and Modeling, 60(10):4881-4893.

Abstract

The fragment docking program solvation energy for exhaustive docking (SEED) is evaluated on 15 different protein targets, with a focus on enrichment and the hit rate. It is shown that SEED allows for consistent computational enrichment of fragment libraries, independent of the effective hit rate. Depending on the actual target protein, true positive rates ranging up to 27% are observed at a cutoff value corresponding to the experimental hit rate. The impact of variations in docking protocols and energy filters is discussed in detail. Remaining issues, limitations, and use cases of SEED are also discussed. Our results show that fragment library selection or enhancement for a particular target is likely to benefit from docking with SEED, suggesting that SEED is a useful resource for fragment screening campaigns. A workflow is presented for the use of the program in virtual screening, including filtering and postprocessing to optimize hit rates.

Abstract

The fragment docking program solvation energy for exhaustive docking (SEED) is evaluated on 15 different protein targets, with a focus on enrichment and the hit rate. It is shown that SEED allows for consistent computational enrichment of fragment libraries, independent of the effective hit rate. Depending on the actual target protein, true positive rates ranging up to 27% are observed at a cutoff value corresponding to the experimental hit rate. The impact of variations in docking protocols and energy filters is discussed in detail. Remaining issues, limitations, and use cases of SEED are also discussed. Our results show that fragment library selection or enhancement for a particular target is likely to benefit from docking with SEED, suggesting that SEED is a useful resource for fragment screening campaigns. A workflow is presented for the use of the program in virtual screening, including filtering and postprocessing to optimize hit rates.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Physical Sciences > General Chemistry
Physical Sciences > General Chemical Engineering
Physical Sciences > Computer Science Applications
Social Sciences & Humanities > Library and Information Sciences
Language:English
Date:26 October 2020
Deposited On:18 Nov 2020 16:05
Last Modified:18 Nov 2020 16:09
Publisher:American Chemical Society (ACS)
ISSN:1549-9596
OA Status:Closed
Publisher DOI:https://doi.org/10.1021/acs.jcim.0c00556
PubMed ID:32820916

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