Assessment of the fragment docking program SEED

TitleAssessment of the fragment docking program SEED
Publication TypeJournal Article
Year of Publication2020
AuthorsGoossens K., Wroblowski B., Langini C., Van Vlijmen H., Caflisch A., De Winter H.
JournalJournal of Chemical Information and Modeling
Date Published2020 Aug 21
Type of ArticleResearch Article
ISSN1549-960X
Abstract

The fragment docking program SEED (Solvation Energy for Exhaustive Docking) is evaluated on 15 different protein targets, with a focus on enrichment and 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 from 5% to 28% are observed at a cutoff value corresponding to the experimental hit rate. The impact of variations in docking protocols and energy filters are 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 post-processing to optimize hit rates.

DOI10.1021/acs.jcim.0c00556
pubindex

0256

Alternate JournalJ. Chem. Inf. Model.
PubMed ID32820916