In Silico Veritas: The Pitfalls and Challenges of Predicting GPCR-Ligand Interactions
Recently the first community-wide assessments of the prediction of the structures of complexes between proteins and small molecule ligands have been reported in the so-called GPCR Dock 2008 and 2010 assessments. In the current review we discuss the different steps along the protein-ligand modeling w...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2011-09-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1424-8247/4/9/1196/ |
| _version_ | 1818299131090698240 |
|---|---|
| author | Sander B. Nabuurs Jan P.G. Klomp Rob Leurs Jacob De Vlieg Iwan J.P. De Esch Bas Vroling Marijn P.A. Sanders Luc Roumen Chris De Graaf |
| author_facet | Sander B. Nabuurs Jan P.G. Klomp Rob Leurs Jacob De Vlieg Iwan J.P. De Esch Bas Vroling Marijn P.A. Sanders Luc Roumen Chris De Graaf |
| author_sort | Sander B. Nabuurs |
| collection | DOAJ |
| description | Recently the first community-wide assessments of the prediction of the structures of complexes between proteins and small molecule ligands have been reported in the so-called GPCR Dock 2008 and 2010 assessments. In the current review we discuss the different steps along the protein-ligand modeling workflow by critically analyzing the modeling strategies we used to predict the structures of protein-ligand complexes we submitted to the recent GPCR Dock 2010 challenge. These representative test cases, focusing on the pharmaceutically relevant G Protein-Coupled Receptors, are used to demonstrate the strengths and challenges of the different modeling methods. Our analysis indicates that the proper performance of the sequence alignment, introduction of structural adjustments guided by experimental data, and the usage of experimental data to identify protein-ligand interactions are critical steps in the protein-ligand modeling protocol. |
| first_indexed | 2024-12-13T04:46:20Z |
| format | Article |
| id | doaj.art-b817a1a6078842f9b85b0a7b3d4636bb |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-12-13T04:46:20Z |
| publishDate | 2011-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-b817a1a6078842f9b85b0a7b3d4636bb2022-12-21T23:59:08ZengMDPI AGPharmaceuticals1424-82472011-09-01491196121510.3390/ph4091196In Silico Veritas: The Pitfalls and Challenges of Predicting GPCR-Ligand InteractionsSander B. NabuursJan P.G. KlompRob LeursJacob De VliegIwan J.P. De EschBas VrolingMarijn P.A. SandersLuc RoumenChris De GraafRecently the first community-wide assessments of the prediction of the structures of complexes between proteins and small molecule ligands have been reported in the so-called GPCR Dock 2008 and 2010 assessments. In the current review we discuss the different steps along the protein-ligand modeling workflow by critically analyzing the modeling strategies we used to predict the structures of protein-ligand complexes we submitted to the recent GPCR Dock 2010 challenge. These representative test cases, focusing on the pharmaceutically relevant G Protein-Coupled Receptors, are used to demonstrate the strengths and challenges of the different modeling methods. Our analysis indicates that the proper performance of the sequence alignment, introduction of structural adjustments guided by experimental data, and the usage of experimental data to identify protein-ligand interactions are critical steps in the protein-ligand modeling protocol.http://www.mdpi.com/1424-8247/4/9/1196/comparative modelingligand binding mode predictionG protein-coupled receptor (GPCR)GPCR Dock 2010 |
| spellingShingle | Sander B. Nabuurs Jan P.G. Klomp Rob Leurs Jacob De Vlieg Iwan J.P. De Esch Bas Vroling Marijn P.A. Sanders Luc Roumen Chris De Graaf In Silico Veritas: The Pitfalls and Challenges of Predicting GPCR-Ligand Interactions Pharmaceuticals comparative modeling ligand binding mode prediction G protein-coupled receptor (GPCR) GPCR Dock 2010 |
| title | In Silico Veritas: The Pitfalls and Challenges of Predicting GPCR-Ligand Interactions |
| title_full | In Silico Veritas: The Pitfalls and Challenges of Predicting GPCR-Ligand Interactions |
| title_fullStr | In Silico Veritas: The Pitfalls and Challenges of Predicting GPCR-Ligand Interactions |
| title_full_unstemmed | In Silico Veritas: The Pitfalls and Challenges of Predicting GPCR-Ligand Interactions |
| title_short | In Silico Veritas: The Pitfalls and Challenges of Predicting GPCR-Ligand Interactions |
| title_sort | in silico veritas the pitfalls and challenges of predicting gpcr ligand interactions |
| topic | comparative modeling ligand binding mode prediction G protein-coupled receptor (GPCR) GPCR Dock 2010 |
| url | http://www.mdpi.com/1424-8247/4/9/1196/ |
| work_keys_str_mv | AT sanderbnabuurs insilicoveritasthepitfallsandchallengesofpredictinggpcrligandinteractions AT janpgklomp insilicoveritasthepitfallsandchallengesofpredictinggpcrligandinteractions AT robleurs insilicoveritasthepitfallsandchallengesofpredictinggpcrligandinteractions AT jacobdevlieg insilicoveritasthepitfallsandchallengesofpredictinggpcrligandinteractions AT iwanjpdeesch insilicoveritasthepitfallsandchallengesofpredictinggpcrligandinteractions AT basvroling insilicoveritasthepitfallsandchallengesofpredictinggpcrligandinteractions AT marijnpasanders insilicoveritasthepitfallsandchallengesofpredictinggpcrligandinteractions AT lucroumen insilicoveritasthepitfallsandchallengesofpredictinggpcrligandinteractions AT chrisdegraaf insilicoveritasthepitfallsandchallengesofpredictinggpcrligandinteractions |