Community-Wide Assessment of Protein-Interface Modeling Suggests Improvements to Design Methodology. - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement
Journal Articles Journal of Molecular Biology Year : 2011

Community-Wide Assessment of Protein-Interface Modeling Suggests Improvements to Design Methodology.

Sarel J Fleishman (1) , Timothy A Whitehead (1) , Eva-Maria Strauch (1) , Jacob E Corn (1) , Sanbo Qin (2) , Huan-Xiang Zhou (2) , Julie C Mitchell (3) , Omar N A Demerdash (3) , Mayuko Takeda-Shitaka (4) , Genki Terashi (4) , Iain H Moal (5) , Xiaofan Li (5) , Paul A Bates (5) , Martin Zacharias (6) , Hahnbeom Park (7) , Jun-Su Ko (7) , Hasup Lee (7) , Chaok Seok (7) , Thomas Bourquard (8) , Julie Bernauer (9) , Anne Poupon (10) , Jérôme Azé (9) , Seren Soner (11) , Sefik Kerem Ovali (11) , Pemra Ozbek (11) , Nir Ben Tal (12) , Türkan Haliloglu (11) , Howook Hwang (13) , Thom Vreven (13) , Brian G Pierce (13) , Zhiping Weng (13) , Laura Pérez-Cano (14) , Carles Pons (14) , Juan Fernández-Recio (14) , Fan Jiang (15) , Feng Yang (16) , Xinqi Gong (16) , Libin Cao (16) , Xianjin Xu (16) , Bin Liu (16) , Panwen Wang (16) , Chunhua Li (16) , Cunxin Wang (16) , Charles H Robert (17) , Mainak Guharoy (17) , Shiyong Liu (18) , Yangyu Huang (18) , Lin Li (18) , Dachuan Guo (18) , Ying Chen (18) , Yi Xiao (18) , Nir London (19) , Zohar Itzhaki (19) , Ora Schueler-Furman (19) , Yuval Inbar (20) , Vladimir Patapov (20) , Mati Cohen (20) , Gideon Schreiber (20) , Yuko Tsuchiya (21) , Eiji Kanamori (22) , Daron M Standley (23) , Haruki Nakamura (21) , Kengo Kinoshita (24) , Camden M Driggers (25) , Robert G Hall (25) , Jessica L Morgan (25) , Victor L Hsu (25) , Jian Zhan (26) , Yuedong Yang (26) , Yaoqi Zhou (26) , Panagiotis L Kastritis (27) , Alexandre M J J Bonvin (27) , Weiyi Zhang (28) , Carlos J Camacho (28) , Krishna P Kilambi (29) , Aroop Sircar (29) , Jeffrey J Gray (29) , Masahito Ohue (30) , Nobuyuki Uchikoga (30) , Yuri Matsuzaki (30) , Takashi Ishida (30) , Yutaka Akiyama (30) , Raed Khashan (31) , Stephen Bush (31) , Denis Fouches (31) , Alexander Tropsha (31) , Juan Esquivel-Rodríguez (32) , Daisuke Kihara (32) , P Benjamin Stranges (31) , Ron Jacak (31) , Brian Kuhlman (31) , Sheng-You Huang (33) , Xiaoqin Zou (33) , Shoshana J Wodak (34) , Joel Janin (35) , David Baker (1)
1 University of Washington [Seattle]
2 Institute of Molecular Biophysics [Tallahassee]
3 University of Wisconsin Whitewater
4 Kitasato University
5 Biomolecular Modelling laboratory [London]
6 TUM - Technische Universität Munchen - Technical University Munich - Université Technique de Munich
7 SNU - Seoul National University [Seoul]
8 ORPAILLEUR - Knowledge representation, reasonning
9 AMIB - Algorithms and Models for Integrative Biology
10 PRC - Physiologie de la reproduction et des comportements [Nouzilly]
11 ChE - Department of Chemical Engineering [Bogazici]
12 TAU - Tel Aviv University
13 UMASS - University of Massachusetts Medical School [Worcester]
14 BSC-CNS - Barcelona Supercomputing Center - Centro Nacional de Supercomputacion
15 CAS - Chinese Academy of Sciences [Beijing]
16 Beijing University of Technology
17 LBT (UPR_9080) - Laboratoire de biochimie théorique [Paris]
18 HUST - Huazhong University of Science and Technology [Wuhan]
19 Hadassah Hebrew University Medical Center [Jerusalem]
20 Weizmann Institute of Science [Rehovot, Israël]
21 Institute for Protein Research [Osaka]
22 Japan Biological Informatics Consortium [Tokyo]
23 IFREC - WPI Immunology Frontier Research Center
24 Graduate School of Information Sciences [Sendai]
25 OSU - Oregon State University
26 IUPUI - Indiana University - Purdue University Indianapolis
27 Bijvoet Center for Biomolecular Research [Utrecht]
28 PITT - University of Pittsburgh
29 JHU - Johns Hopkins University
30 TITECH - Tokyo Institute of Technology [Tokyo]
31 UNC - University of North Carolina [Chapel Hill]
32 Purdue University [West Lafayette]
33 Dalton Cardiovascular Research Center [Columbia]
34 SickKids - The Hospital for sick children [Toronto]
35 IBBMC - Institut de biochimie et biophysique moléculaire et cellulaire
Chaok Seok
Nir Ben Tal
  • Function : Author
Fan Jiang
Feng Yang
Takashi Ishida
Daisuke Kihara
David Baker

Abstract

The CAPRI (Critical Assessment of Predicted Interactions) and CASP (Critical Assessment of protein Structure Prediction) experiments have demonstrated the power of community-wide tests of methodology in assessing the current state of the art and spurring progress in the very challenging areas of protein docking and structure prediction. We sought to bring the power of community-wide experiments to bear on a very challenging protein design problem that provides a complementary but equally fundamental test of current understanding of protein-binding thermodynamics. We have generated a number of designed protein-protein interfaces with very favorable computed binding energies but which do not appear to be formed in experiments, suggesting that there may be important physical chemistry missing in the energy calculations. A total of 28 research groups took up the challenge of determining what is missing: we provided structures of 87 designed complexes and 120 naturally occurring complexes and asked participants to identify energetic contributions and/or structural features that distinguish between the two sets. The community found that electrostatics and solvation terms partially distinguish the designs from the natural complexes, largely due to the nonpolar character of the designed interactions. Beyond this polarity difference, the community found that the designed binding surfaces were, on average, structurally less embedded in the designed monomers, suggesting that backbone conformational rigidity at the designed surface is important for realization of the designed function. These results can be used to improve computational design strategies, but there is still much to be learned; for example, one designed complex, which does form in experiments, was classified by all metrics as a nonbinder.

Dates and versions

inria-00637848 , version 1 (03-11-2011)

Identifiers

Cite

Sarel J Fleishman, Timothy A Whitehead, Eva-Maria Strauch, Jacob E Corn, Sanbo Qin, et al.. Community-Wide Assessment of Protein-Interface Modeling Suggests Improvements to Design Methodology.. Journal of Molecular Biology, 2011, 414 (2), in press. ⟨10.1016/j.jmb.2011.09.031⟩. ⟨inria-00637848⟩
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