System among the corticosteroids: Specificity and molecular dynamics
Understanding how structural features determine specific biological activities has often proved elusive. With over 161 000 steroid structures described, an algorithm able to predict activity from structural attributes would provide manifest benefits. Molecular simulations of a range of 35 corticoste...
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2012
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17425689_v9_n66_p43_Brookes http://hdl.handle.net/20.500.12110/paper_17425689_v9_n66_p43_Brookes |
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paper:paper_17425689_v9_n66_p43_Brookes2023-06-08T16:27:08Z System among the corticosteroids: Specificity and molecular dynamics Aldosterone Conformational mobility Cortisol Deoxycorticosterone Glucocorticoid Mineralocorticoid Molecular dynamics Aldosterone Conformational mobility Cortisol Deoxycorticosterone Glucocorticoid Mineralocorticoid Drug products aldosterone betamethasone corticosteroid corticosteroid antagonist corticosterone deoxycorticosterone dexamethasone fludrocortisone glucocorticoid hydrocortisone mineralocorticoid prednisolone prednisone triamcinolone article drug activity drug mechanism molecular dynamics Understanding how structural features determine specific biological activities has often proved elusive. With over 161 000 steroid structures described, an algorithm able to predict activity from structural attributes would provide manifest benefits. Molecular simulations of a range of 35 corticosteroids show striking correlations between conformational mobility and biological specificity. Thus steroid ring A is important for glucocorticoid action, and is rigid in the most specific (and potent) examples, such as dexamethasone. By contrast, ring C conformation is important for the mineralocorticoids, and is rigid in aldosterone. Other steroids that are less specific, or have mixed functions, or none at all, are more flexible. One unexpected example is 11-deoxycorticosterone, which the methods predict (and our activity studies confirm) is not only a specific mineralocorticoid, but also has significant glucocorticoid activity. These methods may guide the design of new corticosteroid agonists and antagonists. They will also have application in other examples of ligand-receptor interactions. This journal is © 2011 The Royal Society. 2012 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17425689_v9_n66_p43_Brookes http://hdl.handle.net/20.500.12110/paper_17425689_v9_n66_p43_Brookes |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Aldosterone Conformational mobility Cortisol Deoxycorticosterone Glucocorticoid Mineralocorticoid Molecular dynamics Aldosterone Conformational mobility Cortisol Deoxycorticosterone Glucocorticoid Mineralocorticoid Drug products aldosterone betamethasone corticosteroid corticosteroid antagonist corticosterone deoxycorticosterone dexamethasone fludrocortisone glucocorticoid hydrocortisone mineralocorticoid prednisolone prednisone triamcinolone article drug activity drug mechanism molecular dynamics |
| spellingShingle |
Aldosterone Conformational mobility Cortisol Deoxycorticosterone Glucocorticoid Mineralocorticoid Molecular dynamics Aldosterone Conformational mobility Cortisol Deoxycorticosterone Glucocorticoid Mineralocorticoid Drug products aldosterone betamethasone corticosteroid corticosteroid antagonist corticosterone deoxycorticosterone dexamethasone fludrocortisone glucocorticoid hydrocortisone mineralocorticoid prednisolone prednisone triamcinolone article drug activity drug mechanism molecular dynamics System among the corticosteroids: Specificity and molecular dynamics |
| topic_facet |
Aldosterone Conformational mobility Cortisol Deoxycorticosterone Glucocorticoid Mineralocorticoid Molecular dynamics Aldosterone Conformational mobility Cortisol Deoxycorticosterone Glucocorticoid Mineralocorticoid Drug products aldosterone betamethasone corticosteroid corticosteroid antagonist corticosterone deoxycorticosterone dexamethasone fludrocortisone glucocorticoid hydrocortisone mineralocorticoid prednisolone prednisone triamcinolone article drug activity drug mechanism molecular dynamics |
| description |
Understanding how structural features determine specific biological activities has often proved elusive. With over 161 000 steroid structures described, an algorithm able to predict activity from structural attributes would provide manifest benefits. Molecular simulations of a range of 35 corticosteroids show striking correlations between conformational mobility and biological specificity. Thus steroid ring A is important for glucocorticoid action, and is rigid in the most specific (and potent) examples, such as dexamethasone. By contrast, ring C conformation is important for the mineralocorticoids, and is rigid in aldosterone. Other steroids that are less specific, or have mixed functions, or none at all, are more flexible. One unexpected example is 11-deoxycorticosterone, which the methods predict (and our activity studies confirm) is not only a specific mineralocorticoid, but also has significant glucocorticoid activity. These methods may guide the design of new corticosteroid agonists and antagonists. They will also have application in other examples of ligand-receptor interactions. This journal is © 2011 The Royal Society. |
| title |
System among the corticosteroids: Specificity and molecular dynamics |
| title_short |
System among the corticosteroids: Specificity and molecular dynamics |
| title_full |
System among the corticosteroids: Specificity and molecular dynamics |
| title_fullStr |
System among the corticosteroids: Specificity and molecular dynamics |
| title_full_unstemmed |
System among the corticosteroids: Specificity and molecular dynamics |
| title_sort |
system among the corticosteroids: specificity and molecular dynamics |
| publishDate |
2012 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17425689_v9_n66_p43_Brookes http://hdl.handle.net/20.500.12110/paper_17425689_v9_n66_p43_Brookes |
| _version_ |
1768545758736285696 |