Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment: meeting new challenges

Research output: Contribution to journalJournal articleResearchpeer-review

Irina Kufareva, Vsevolod Katritch, Phil Biggin, Minsup Kim, Kichul Park, Sang Won Jung, Art E. Cho, Zara A. Sands, Liliana Ostopovici-Halip, Cristian G. Bologa, Christoffer Norn, Michal Brylinski, Jeffrey Skolnick, Henrik Keränen, Bart E. Lenselink, Gerard Van Westen, John P. Overington, Hugo Gutiérrez De Teráán, Vignir Isberg, Kimberley M. Fidom & 96 others Thomas M. Lehto, David E. Gloriam, Anirban Ghosh, Uddhavesh Sonavane, Rajendra Joshi, Jie Xia, Jui Hua Hsieh, Liangren Zhang, Xiang Simon Wang, Horst Vogel, Shuguang Yuan, X. Feng, M. Chen, J. Ambia, P. Barth, Cédric Gageat, Michal Stepniewski, Henri Xhaard, Sebastian Kelm, William R. Pitt, Jiye Shi, Adrien Larsen, Hubert Li, Jeffrey Wagner, Supriyo Bhattacharya, Nagarajan Vaidehi, Kazuhiko Kanou, Vaclav Cvicek, Soo Kyung Kim, Bartosz Trzaskowski, William A. Goddard, Ravinder Abrol, Balaji Selvam, Irina G. Tikhonova, Alberto Cuzzolin, Davide Sabbadin, Antonella Ciancetta, Stefano Moro, Thibaud Freyd, Mari Gabrielsen, Kurt Kristiansen, Ingebrigt Sylte, Kevin J. Gaffney, Nicos A. Petasis, Dorota Latek, Marek Bajda, Krzysztof Młynarczyk, Sławomir Filipek, Laura López, Michael Kuiper, Thijs Beuming, Jose Manuel Perez-Aguilar, Ray Yu Ruei Wang, Hahnbeom Park, Per Greisen, Yifan Song, Frank DiMaio, David Baker, Woong Hee Shin, Lim Heo, Gyu Rie Lee, Chaok Seok, Jianyi Yang, Yang Zhang, Marco Ponassi, Camillo Rosano, Georgy Cheremovskiy, Sergei Grudinin, Rajan Chaudhari, Andrew J. Heim, Zhijun Li, Qiang Lv, Martin G. Grigorov, Xin Hu, Hongmao Sun, Min Shen, Noel Southall, Ajit Jadhav, David Rodríguez, Anirudh Ranganathan, Jens Carlsson, Rafael Najmanovich, Serdar Durdagi, Claire De March, Julien Diharce, Jérôme Golebiowski, Serge Antonczak, Sébastien Fiorucci, Elizabeth Nguyen, Jens Meiler, Aleksandrs Gutcaits, Maria Marti-Solano, Manuel Pastor, Jana Selent, Raymond C. Stevens, Ruben Abagyan

Despite tremendous successes of GPCR crystallography, the receptors with available structures represent only a small fraction of human GPCRs. An important role of the modeling community is to maximize structural insights for the remaining receptors and complexes. The community-wide GPCR Dock assessment was established to stimulate and monitor the progress in molecular modeling and ligand docking for GPCRs. The four targets in the present third assessment round presented new and diverse challenges for modelers, including prediction of allosteric ligand interaction and activation states in 5-hydroxytryptamine receptors 1B and 2B, and modeling by extremely distant homology for smoothened receptor. Forty-four modeling groups participated in the assessment. State-of-the-art modeling approaches achieved close-to-experimental accuracy for small rigid orthosteric ligands and models built by close homology, and they correctly predicted protein fold for distant homology targets. Predictions of long loops and GPCR activation states remain unsolved problems.

Original languageEnglish
JournalStructure
Volume22
Issue number8
Pages (from-to)1120-1139
Number of pages20
ISSN0969-2126
DOIs
Publication statusPublished - 2014

ID: 165017646