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

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; 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

doi:10.1016/j.str.2014.06.012

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

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. FidomThomas 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

^*Corresponding author for this work

128 Citations (Scopus)

Abstract

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 language	English
Journal	Structure
Volume	22
Issue number	8
Pages (from-to)	1120-1139
Number of pages	20
ISSN	0969-2126
DOIs	https://doi.org/10.1016/j.str.2014.06.012
Publication status	Published - 2014

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Kufareva, I., Katritch, V., Biggin, P., Kim, M., Park, K., Jung, S. W., Cho, A. E., Sands, Z. A., Ostopovici-Halip, L., Bologa, C. G., Norn, C., Brylinski, M., Skolnick, J., Keränen, H., Lenselink, B. E., Van Westen, G., Overington, J. P., De Teráán, H. G., Isberg, V., ... Abagyan, R. (2014). Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment: meeting new challenges. Structure, 22(8), 1120-1139. https://doi.org/10.1016/j.str.2014.06.012

Kufareva, I, Katritch, V, Biggin, P, Kim, M, Park, K, Jung, SW, Cho, AE, Sands, ZA, Ostopovici-Halip, L, Bologa, CG, Norn, C, Brylinski, M, Skolnick, J, Keränen, H, Lenselink, BE, Van Westen, G, Overington, JP, De Teráán, HG, Isberg, V, Fidom, KM, Lehto, TM, Gloriam, DE, Ghosh, A, Sonavane, U, Joshi, R, Xia, J, Hsieh, JH, Zhang, L, Wang, XS, Vogel, H, Yuan, S, Feng, X, Chen, M, Ambia, J, Barth, P, Gageat, C, Stepniewski, M, Xhaard, H, Kelm, S, Pitt, WR, Shi, J, Larsen, A, Li, H, Wagner, J, Bhattacharya, S, Vaidehi, N, Kanou, K, Cvicek, V, Kim, SK, Trzaskowski, B, Goddard, WA, Abrol, R, Selvam, B, Tikhonova, IG, Cuzzolin, A, Sabbadin, D, Ciancetta, A, Moro, S, Freyd, T, Gabrielsen, M, Kristiansen, K, Sylte, I, Gaffney, KJ, Petasis, NA, Latek, D, Bajda, M, Młynarczyk, K, Filipek, S, López, L, Kuiper, M, Beuming, T, Perez-Aguilar, JM, Wang, RYR, Park, H, Greisen, P, Song, Y, DiMaio, F, Baker, D, Shin, WH, Heo, L, Lee, GR, Seok, C, Yang, J, Zhang, Y, Ponassi, M, Rosano, C, Cheremovskiy, G, Grudinin, S, Chaudhari, R, Heim, AJ, Li, Z, Lv, Q, Grigorov, MG, Hu, X, Sun, H, Shen, M, Southall, N, Jadhav, A, Rodríguez, D, Ranganathan, A, Carlsson, J, Najmanovich, R, Durdagi, S, De March, C, Diharce, J, Golebiowski, J, Antonczak, S, Fiorucci, S, Nguyen, E, Meiler, J, Gutcaits, A, Marti-Solano, M, Pastor, M, Selent, J, Stevens, RC & Abagyan, R 2014, 'Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment: meeting new challenges', Structure, vol. 22, no. 8, pp. 1120-1139. https://doi.org/10.1016/j.str.2014.06.012

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title = "Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment: meeting new challenges",

abstract = "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.",

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

year = "2014",

doi = "10.1016/j.str.2014.06.012",

language = "English",

volume = "22",

pages = "1120--1139",

journal = "Structure",

issn = "0969-2126",

publisher = "Cell Press",

number = "8",

}

TY - JOUR

T1 - Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment

T2 - meeting new challenges

AU - Kufareva, Irina

AU - Katritch, Vsevolod

AU - Biggin, Phil

AU - Kim, Minsup

AU - Park, Kichul

AU - Jung, Sang Won

AU - Cho, Art E.

AU - Sands, Zara A.

AU - Ostopovici-Halip, Liliana

AU - Bologa, Cristian G.

AU - Norn, Christoffer

AU - Brylinski, Michal

AU - Skolnick, Jeffrey

AU - Keränen, Henrik

AU - Lenselink, Bart E.

AU - Van Westen, Gerard

AU - Overington, John P.

AU - De Teráán, Hugo Gutiérrez

AU - Isberg, Vignir

AU - Fidom, Kimberley M.

AU - Lehto, Thomas M.

AU - Gloriam, David E.

AU - Ghosh, Anirban

AU - Sonavane, Uddhavesh

AU - Joshi, Rajendra

AU - Xia, Jie

AU - Hsieh, Jui Hua

AU - Zhang, Liangren

AU - Wang, Xiang Simon

AU - Vogel, Horst

AU - Yuan, Shuguang

AU - Feng, X.

AU - Chen, M.

AU - Ambia, J.

AU - Barth, P.

AU - Gageat, Cédric

AU - Stepniewski, Michal

AU - Xhaard, Henri

AU - Kelm, Sebastian

AU - Pitt, William R.

AU - Shi, Jiye

AU - Larsen, Adrien

AU - Li, Hubert

AU - Wagner, Jeffrey

AU - Bhattacharya, Supriyo

AU - Vaidehi, Nagarajan

AU - Kanou, Kazuhiko

AU - Cvicek, Vaclav

AU - Kim, Soo Kyung

AU - Trzaskowski, Bartosz

AU - Goddard, William A.

AU - Abrol, Ravinder

AU - Selvam, Balaji

AU - Tikhonova, Irina G.

AU - Cuzzolin, Alberto

AU - Sabbadin, Davide

AU - Ciancetta, Antonella

AU - Moro, Stefano

AU - Freyd, Thibaud

AU - Gabrielsen, Mari

AU - Kristiansen, Kurt

AU - Sylte, Ingebrigt

AU - Gaffney, Kevin J.

AU - Petasis, Nicos A.

AU - Latek, Dorota

AU - Bajda, Marek

AU - Młynarczyk, Krzysztof

AU - Filipek, Sławomir

AU - López, Laura

AU - Kuiper, Michael

AU - Beuming, Thijs

AU - Perez-Aguilar, Jose Manuel

AU - Wang, Ray Yu Ruei

AU - Park, Hahnbeom

AU - Greisen, Per

AU - Song, Yifan

AU - DiMaio, Frank

AU - Baker, David

AU - Shin, Woong Hee

AU - Heo, Lim

AU - Lee, Gyu Rie

AU - Seok, Chaok

AU - Yang, Jianyi

AU - Zhang, Yang

AU - Ponassi, Marco

AU - Rosano, Camillo

AU - Cheremovskiy, Georgy

AU - Grudinin, Sergei

AU - Chaudhari, Rajan

AU - Heim, Andrew J.

AU - Li, Zhijun

AU - Lv, Qiang

AU - Grigorov, Martin G.

AU - Hu, Xin

AU - Sun, Hongmao

AU - Shen, Min

AU - Southall, Noel

AU - Jadhav, Ajit

AU - Rodríguez, David

AU - Ranganathan, Anirudh

AU - Carlsson, Jens

AU - Najmanovich, Rafael

AU - Durdagi, Serdar

AU - De March, Claire

AU - Diharce, Julien

AU - Golebiowski, Jérôme

AU - Antonczak, Serge

AU - Fiorucci, Sébastien

AU - Nguyen, Elizabeth

AU - Meiler, Jens

AU - Gutcaits, Aleksandrs

AU - Marti-Solano, Maria

AU - Pastor, Manuel

AU - Selent, Jana

AU - Stevens, Raymond C.

AU - Abagyan, Ruben

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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U2 - 10.1016/j.str.2014.06.012

DO - 10.1016/j.str.2014.06.012

M3 - Journal article

C2 - 25066135

AN - SCOPUS:84905732337

SN - 0969-2126

VL - 22

SP - 1120

EP - 1139

JO - Structure

JF - Structure

IS - 8

ER -

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

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