English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

How accurate do structures of the β 2 adrenergic receptor (β 2 AR) need to be to effectively serve as platforms for docking-based virtual screening campaigns? To answer this research question, here, we targeted through controlled virtual screening experiments 23 homology models of the β 2 AR endowed with different levels of structural accuracy. Subsequently, we studied the correlation between virtual screening performance and structural accuracy of the targeted models. Moreover, we studied the correlation between virtual screening performance and template/target receptor sequence identity. Our study demonstrates that docking-based virtual screening campaigns targeting homology models of the β 2 AR, in the majority of the cases, yielded results that exceeded random expectations in terms of area under the receiver operating characteristic curve (ROC AUC). Moreover, with the most effective scoring method, over one-third and one-quarter of the models yielded results that exceeded random expectation also in terms of enrichment factors (EF1, EF5, and EF10) and BEDROC (α = 160.9), respectively. Not surprisingly, we found a detectable linear correlation between virtual screening performance and structural accuracy of the ligand-binding cavity. We also found a detectable linear correlation between virtual screening performance and structural accuracy of the second extracellular loop (EL2). Finally, our data indicate that, although there is no detectable linear correlation between virtual screening performance and template/β 2 AR sequence identity, models built on the basis of templates that show high sequence identity with the β 2 AR, especially within the ligand-biding cavity, performed consistently well. Conversely, models with lower sequence identity displayed performance levels that ranged from very good to random, with no apparent correlation with the sequence identity itself.

journal of chemical information and modeling

Influence of the Structural Accuracy of Homology Models on Their Applicability to Docking-Based Virtual Screening: The β<sub>2</sub> Adrenergic Receptor as a Case Study

Influence of the Structural Accuracy of Homology Models on Their Applicability to Docking-Based Virtual Screening: The β2 Adrenergic Receptor as a Case Study

Influence of the Structural Accuracy of Homology Models on Their Applicability to Docking-Based Virtual Screening: The β₂ Adrenergic Receptor as a Case Study