Name
Title | ||
|---|---|---|
Detection of ligand binding hot spots on protein surfaces via fragment-based methods: application to DJ-1 and glucocerebrosidase. |
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. |
Year | DOI | Venue |
|---|---|---|
2009 | 10.1007/s10822-009-9283-2 | Journal of computer-aided molecular design |
Keywords | Field | DocType |
Fragment-based drug design,Structure-based drug design,Hot spot identification,DJ-1,Glucocerebrosidase,Parkinson’s disease,Gaucher’s disease,Pharmacological chaperones | Plasma protein binding,Drug discovery,Binding site,Glucocerebrosidase,Ligand (biochemistry),Chemistry,Small Molecule Libraries,Bioinformatics,Chaperone (protein),Protein structure | Journal |
Volume | Issue | ISSN |
23 | 8 | 1573-4951 |
Citations | PageRank | References |
8 | 0.73 | 1 |
Authors | ||
13 | ||
Name | Order | Citations | PageRank |
|---|---|---|---|
| Melissa R. Landon | 1 | 55 | 4.66 |
| Raquel L. Lieberman | 2 | 8 | 0.73 |
| Quyen Q. Hoang | 3 | 8 | 0.73 |
| Shulin Ju | 4 | 8 | 0.73 |
| Jose M. M. Caaveiro | 5 | 8 | 0.73 |
| Susan D. Orwig | 6 | 8 | 0.73 |
| Dima Kozakov | 7 | 131 | 15.72 |
| Ryan Brenke | 8 | 54 | 4.63 |
| Gwo-Yu Chuang | 9 | 72 | 7.25 |
| Dmitri Beglov | 10 | 72 | 7.49 |
| Sandor Vajda | 11 | 270 | 34.39 |
| Gregory A. Petsko | 12 | 8 | 0.73 |
| Dagmar Ringe | 13 | 8 | 1.74 |