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Application of a simple quantum chemical approach to ligand fragment scoring for Trypanosoma brucei pteridine reductase 1 inhibition

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dc.abstract.enThere is a need for improved and generally applicable scoring functions for fragment-based approaches to ligand design. Here, we evaluate the performance of a computationally efficient model for inhibitory activity estimation, which is composed only of multipole electrostatic energy and dispersion energy terms that approximate long-range ab initio quantum mechanical interaction energies. We find that computed energies correlate well with inhibitory activity for a compound series with varying substituents targeting two subpockets of the binding site of Trypanosoma brucei pteridine reductase 1. For one subpocket, we find that the model is more predictive for inhibitory activity than the ab initio interaction energy calculated at the MP2 level. Furthermore, the model is found to outperform a commonly used empirical scoring method. Finally, we show that the results for the two subpockets can be combined, which suggests that this simple nonempirical scoring function could be applied in fragment--based drug design.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorWade, Rebecca
dc.contributor.authorPanecka-Hofman, Joanna
dc.contributor.authorJedwabny, Wiktoria
dc.contributor.authorDyguda-Kazimierowicz, Edyta
dc.contributor.authorSOKALSKI, WACŁAW
dc.date.accessioned2024-01-24T16:44:26Z
dc.date.available2024-01-24T16:44:26Z
dc.date.issued2017
dc.description.financeNie dotyczy
dc.identifier.doi10.1007/S10822-017-0035-4
dc.identifier.issn0920-654X
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/100991
dc.languageeng
dc.pbn.affiliationphysical sciences
dc.relation.ispartofJournal of Computer-Aided Molecular Design
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.titleApplication of a simple quantum chemical approach to ligand fragment scoring for Trypanosoma brucei pteridine reductase 1 inhibition
dc.typeJournalArticle
dspace.entity.typePublication