J Chem Inf Model - Boosting virtual screening enrichments with data fusion: coalescing hits from two-dimensional fingerprints, shape, and docking.

Tópicos

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Resumo

Virtual screening is an effective way to find hits in drug discovery, with approaches ranging from fast information-based similarity methods to more computationally intensive physics-based docking methods. However, the best approach to use for a given project is not clear in advance of the screen. In this work, we show that combining results from multiple methods using a standard score (Z-score) can significantly improve virtual screening enrichments over any of the single screening methods. We show that an augmented Z-score, which considers the best two out of three scores for a given compound, outperforms previously published data fusion algorithms. We use three different virtual screening methods (two-dimensional (2D) fingerprint similarity, shape-based similarity, and docking) and study two different databases (DUD and MDDR). The average enrichment in the top 1% was improved by 9% for DUD and 25% for the MDDR, compared with the top individual method. Improvements of 22% for DUD and 43% for MDDR are seen over the average of the three individual methods. Statistics are presented that show a high significance associated with the findings in this work.

Resumo Limpo

virtual screen effect way find hit drug discoveri approach rang fast informationbas similar method comput intens physicsbas dock method howev best approach use given project clear advanc screen work show combin result multipl method use standard score zscore can signific improv virtual screen enrich singl screen method show augment zscore consid best two three score given compound outperform previous publish data fusion algorithm use three differ virtual screen method twodimension d fingerprint similar shapebas similar dock studi two differ databas dud mddr averag enrich top improv dud mddr compar top individu method improv dud mddr seen averag three individu method statist present show high signific associ find work

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