抄録
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.
| 元の言語 | 英語 |
|---|---|
| ページ（範囲） | 491-500 |
| ページ数 | 10 |
| ジャーナル | Journal of Computer-Aided Molecular Design |
| 巻 | 23 |
| 発行部数 | 8 |
| DOI | |
| 出版物ステータス | 出版済み - 6 15 2009 |
| 外部発表 | Yes |
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All Science Journal Classification (ASJC) codes
- Drug Discovery
- Computer Science Applications
- Physical and Theoretical Chemistry
これを引用
Detection of ligand binding hot spots on protein surfaces via fragment-based methods : Application to DJ-1 and glucocerebrosidase. / Landon, Melissa R.; Lieberman, Raquel L.; Hoang, Quyen Q.; Ju, Shulin; Martinez Caaveiro, Jose Manuel; Orwig, Susan D.; Kozakov, Dima; Brenke, Ryan; Chuang, Gwo Yu; Beglov, Dmitry; Vajda, Sandor; Petsko, Gregory A.; Ringe, Dagmar.
：: Journal of Computer-Aided Molecular Design, 巻 23, 番号 8, 15.06.2009, p. 491-500.研究成果: ジャーナルへの寄稿 › 記事
}
TY - JOUR
T1 - Detection of ligand binding hot spots on protein surfaces via fragment-based methods
T2 - Application to DJ-1 and glucocerebrosidase
AU - Landon, Melissa R.
AU - Lieberman, Raquel L.
AU - Hoang, Quyen Q.
AU - Ju, Shulin
AU - Martinez Caaveiro, Jose Manuel
AU - Orwig, Susan D.
AU - Kozakov, Dima
AU - Brenke, Ryan
AU - Chuang, Gwo Yu
AU - Beglov, Dmitry
AU - Vajda, Sandor
AU - Petsko, Gregory A.
AU - Ringe, Dagmar
PY - 2009/6/15
Y1 - 2009/6/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=67650979223&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67650979223&partnerID=8YFLogxK
U2 - 10.1007/s10822-009-9283-2
DO - 10.1007/s10822-009-9283-2
M3 - Article
C2 - 19521672
AN - SCOPUS:67650979223
VL - 23
SP - 491
EP - 500
JO - Journal of Computer-Aided Molecular Design
JF - Journal of Computer-Aided Molecular Design
SN - 0920-654X
IS - 8
ER -