| Title |
Structure–activity relationships of thiostrepton derivatives: implications for rational drug design
|
|---|---|
| Published in |
Perspectives in Drug Discovery and Design, October 2014
|
| DOI | 10.1007/s10822-014-9797-0 |
| Pubmed ID | |
| Authors |
Antje Wolf, Sebastian Schoof, Sascha Baumann, Hans-Dieter Arndt, Karl N. Kirschner |
| Abstract |
The bacterial ribosome is a major target of naturally occurring thiopeptides antibiotics. Studying thiopeptide (e.g. thiostrepton) binding to the GAR's 23S·L11 ribosomal subunit using docking methods is challenging. Regarding the target, the binding site is composed of a flexible protein-RNA nonbonded interface whose available crystal structure is of medium resolution. Regarding the ligands, the thiopeptides are chemically complex, flexible, and contain macrocycles. In this study we developed a combined MD-docking-MD workflow that allows us to study thiopeptide-23S·L11 binding. It is shown that docking thiostrepton-like ligands to an MD-refined receptor structure instead of the medium resolution crystal leads to better convergence to the native-like docking pose and a better reproduction of experimental binding affinities. By applying an energy decomposition analysis, we identify key structural binding elements within GAR's rRNA-protein binding site and within the ligand structures. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
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 % |
|---|---|---|
| Germany | 1 | 4% |
| Unknown | 24 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Postgraduate | 5 | 20% |
| Student > Ph. D. Student | 4 | 16% |
| Student > Master | 4 | 16% |
| Researcher | 3 | 12% |
| Professor > Associate Professor | 2 | 8% |
| Other | 4 | 16% |
| Unknown | 3 | 12% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 9 | 36% |
| Computer Science | 4 | 16% |
| Agricultural and Biological Sciences | 4 | 16% |
| Biochemistry, Genetics and Molecular Biology | 2 | 8% |
| Unspecified | 1 | 4% |
| Other | 2 | 8% |
| Unknown | 3 | 12% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 05 October 2014.
All research outputs
#17,351,840
of 25,461,852 outputs
Outputs from Perspectives in Drug Discovery and Design
#736
of 949 outputs
Outputs of similar age
#160,058
of 266,376 outputs
Outputs of similar age from Perspectives in Drug Discovery and Design
#5
of 10 outputs
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So far Altmetric has tracked 949 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.3. This one is in the 15th percentile – i.e., 15% of its peers scored the same or lower than it.
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We're also able to compare this research output to 10 others from the same source and published within six weeks on either side of this one. This one has scored higher than 5 of them.