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3D-QSAR study of steroidal and azaheterocyclic human aromatase inhibitors using quantitative profile of protein–ligand interactions

Overview of attention for article published in Journal of Cheminformatics, January 2018
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  • Good Attention Score compared to outputs of the same age (67th percentile)

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Title
3D-QSAR study of steroidal and azaheterocyclic human aromatase inhibitors using quantitative profile of protein–ligand interactions
Published in
Journal of Cheminformatics, January 2018
DOI 10.1186/s13321-017-0253-8
Pubmed ID
Authors

Sehan Lee, Mace G. Barron

Abstract

Aromatase is a member of the cytochrome P450 superfamily responsible for a key step in the biosynthesis of estrogens. As estrogens are involved in the control of important reproduction-related processes, including sexual differentiation and maturation, aromatase is a potential target for endocrine disrupting chemicals as well as breast cancer therapy. In this work, 3D-QSAR combined with quantitative profile of protein-ligand interactions was employed in the identification and characterization of critical steric and electronic features of aromatase-inhibitor complexes and the estimation of their quantitative contribution to inhibition potency. Bioactivity data on pIC50 values of 175 steroidal and 124 azaheterocyclic human aromatase inhibitors (AIs) were used for the 3D-QSAR analysis. For the quantitative description of the effects of the hydrophobic contact and nitrogen-heme-iron coordination on aromatase inhibition, the hydrophobicity density field model and the smallest dual descriptor Δf(r) S were introduced, respectively. The model revealed that hydrophobic contact and nitrogen-heme-iron coordination primarily determines inhibition potency of steroidal and azaheterocyclic AIs, respectively. Moreover, hydrogen bonds with key amino acid residues, in particular Asp309 and Met375, and interaction with the heme-iron are required for potent inhibition. Phe221 and Thr310 appear to be quite flexible and adopt different conformations according to a substituent at 4- or 6-position of steroids. Flexible docking results indicate that proper representation of the residues' flexibility is critical for reasonable description of binding of the structurally diverse inhibitors. Our results provide a quantitative and mechanistic understanding of inhibitory activity of steroidal and azaheterocyclic AIs of relevance to adverse outcome pathway development and rational drug design.

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X Demographics

The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 25 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 5 20%
Researcher 4 16%
Other 2 8%
Student > Ph. D. Student 2 8%
Student > Doctoral Student 1 4%
Other 2 8%
Unknown 9 36%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 16%
Chemistry 4 16%
Pharmacology, Toxicology and Pharmaceutical Science 3 12%
Computer Science 2 8%
Agricultural and Biological Sciences 1 4%
Other 2 8%
Unknown 9 36%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 January 2018.
All research outputs
#7,088,547
of 23,344,526 outputs
Outputs from Journal of Cheminformatics
#580
of 862 outputs
Outputs of similar age
#143,157
of 443,682 outputs
Outputs of similar age from Journal of Cheminformatics
#12
of 14 outputs
Altmetric has tracked 23,344,526 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 862 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.0. This one is in the 32nd percentile – i.e., 32% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 443,682 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 67% of its contemporaries.
We're also able to compare this research output to 14 others from the same source and published within six weeks on either side of this one. This one is in the 21st percentile – i.e., 21% of its contemporaries scored the same or lower than it.