| Title |
Detection of ligand binding hot spots on protein surfaces via fragment-based methods: application to DJ-1 and glucocerebrosidase
|
|---|---|
| Published in |
Perspectives in Drug Discovery and Design, June 2009
|
| DOI | 10.1007/s10822-009-9283-2 |
| Pubmed ID | |
| Authors |
Melissa R. Landon, Raquel L. Lieberman, Quyen Q. Hoang, Shulin Ju, Jose M. M. Caaveiro, Susan D. Orwig, Dima Kozakov, Ryan Brenke, Gwo-Yu Chuang, Dmitry Beglov, Sandor Vajda, Gregory A. Petsko, Dagmar Ringe |
| Abstract |
The identification of hot spots, i.e., binding regions that contribute substantially to the free energy of ligand binding, is a critical step for structure-based drug design. Here we present the application of two fragment-based methods to the detection of hot spots for DJ-1 and glucocerebrosidase (GCase), targets for the development of therapeutics for Parkinson's and Gaucher's diseases, respectively. While the structures of these two proteins are known, binding information is lacking. In this study we employ the experimental multiple solvent crystal structures (MSCS) method and computational fragment mapping (FTMap) to identify regions suitable for the development of pharmacological chaperones for DJ-1 and GCase. Comparison of data derived via MSCS and FTMap also shows that FTMap, a computational method for the identification of fragment binding hot spots, is an accurate and robust alternative to the performance of expensive and difficult crystallographic experiments. |
Mendeley readers
The data shown below were compiled from readership statistics for 126 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 7 | 6% |
| Germany | 2 | 2% |
| Norway | 2 | 2% |
| Denmark | 2 | 2% |
| Taiwan | 1 | <1% |
| Russia | 1 | <1% |
| Japan | 1 | <1% |
| United States | 1 | <1% |
| Serbia | 1 | <1% |
| Other | 0 | 0% |
| Unknown | 108 | 86% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 36 | 29% |
| Student > Ph. D. Student | 30 | 24% |
| Student > Master | 10 | 8% |
| Other | 8 | 6% |
| Professor > Associate Professor | 8 | 6% |
| Other | 21 | 17% |
| Unknown | 13 | 10% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 37 | 29% |
| Chemistry | 31 | 25% |
| Biochemistry, Genetics and Molecular Biology | 15 | 12% |
| Medicine and Dentistry | 7 | 6% |
| Computer Science | 6 | 5% |
| Other | 10 | 8% |
| Unknown | 20 | 16% |
Attention Score in Context
This research output has an Altmetric Attention Score of 11. 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 18 July 2017.
All research outputs
#3,408,630
of 25,461,852 outputs
Outputs from Perspectives in Drug Discovery and Design
#111
of 949 outputs
Outputs of similar age
#12,821
of 123,166 outputs
Outputs of similar age from Perspectives in Drug Discovery and Design
#3
of 17 outputs
Altmetric has tracked 25,461,852 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
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 has done well, scoring higher than 87% of its peers.
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 123,166 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 89% of its contemporaries.
We're also able to compare this research output to 17 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.