Blind prediction of interfacial water positions in CAPRI

Marc F. Lensink, Iain H. Moal, Paul A. Bates, Panagiotis L. Kastritis, Adrien S J Melquiond, Ezgi Karaca, Christophe Schmitz, Marc van Dijk, Alexandre M J J Bonvin, Miriam Eisenstein, Brian Jiménez-García, Solène Grosdidier, Albert Solernou, Laura Pérez-Cano, Chiara Pallara, Juan Fernández-Recio, Jianqing Xu, Pravin Muthu, Krishna Praneeth Kilambi, Jeffrey J GraySergei Grudinin, Georgy Derevyanko, Julie C. Mitchell, John Wieting, Eiji Kanamori, Yuko Tsuchiya, Yoichi Murakami, Joy Sarmiento, Daron M. Standley, Matsuyuki Shirota, Kengo Kinoshita, Haruki Nakamura, Matthieu Chavent, David W. Ritchie, Hahnbeom Park, Junsu Ko, Hasup Lee, Chaok Seok, Yang Shen, Dima Kozakov, Sandor Vajda, Petras J. Kundrotas, Ilya A. Vakser, Brian G. Pierce, Howook Hwang, Thom Vreven, Zhiping Weng, Idit Buch, Efrat Farkash, Haim J. Wolfson, Martin Zacharias, Sanbo Qin, Huan Xiang Zhou, Shen You Huang, Xiaoqin Zou, Justyna A. Wojdyla, Colin Kleanthous, Shoshana J. Wodak

Research output: Contribution to journalArticle

Abstract

We report the first assessment of blind predictions of water positions at protein-protein interfaces, performed as part of the critical assessment of predicted interactions (CAPRI) community-wide experiment. Groups submitting docking predictions for the complex of the DNase domain of colicin E2 and Im2 immunity protein (CAPRI Target 47), were invited to predict the positions of interfacial water molecules using the method of their choice. The predictions-20 groups submitted a total of 195 models-were assessed by measuring the recall fraction of water-mediated protein contacts. Of the 176 high- or medium-quality docking models-a very good docking performance per se-only 44% had a recall fraction above 0.3, and a mere 6% above 0.5. The actual water positions were in general predicted to an accuracy level no better than 1.5 Å, and even in good models about half of the contacts represented false positives. This notwithstanding, three hotspot interface water positions were quite well predicted, and so was one of the water positions that is believed to stabilize the loop that confers specificity in these complexes. Overall the best interface water predictions was achieved by groups that also produced high-quality docking models, indicating that accurate modelling of the protein portion is a determinant factor. The use of established molecular mechanics force fields, coupled to sampling and optimization procedures also seemed to confer an advantage. Insights gained from this analysis should help improve the prediction of protein-water interactions and their role in stabilizing protein complexes.

Original languageEnglish (US)
Pages (from-to)620-632
Number of pages13
JournalProteins
Volume82
Issue number4
DOIs
StatePublished - 2014

Fingerprint

Water
Proteins
Colicins
Molecular mechanics
Deoxyribonucleases
Mechanics
Immunity
Sampling
Molecules
Experiments

Keywords

  • Blind prediction
  • CAPRI
  • Protein docking
  • Protein interface
  • Water

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Molecular Biology

Cite this

Lensink, M. F., Moal, I. H., Bates, P. A., Kastritis, P. L., Melquiond, A. S. J., Karaca, E., ... Wodak, S. J. (2014). Blind prediction of interfacial water positions in CAPRI. Proteins, 82(4), 620-632. https://doi.org/10.1002/prot.24439

Blind prediction of interfacial water positions in CAPRI. / Lensink, Marc F.; Moal, Iain H.; Bates, Paul A.; Kastritis, Panagiotis L.; Melquiond, Adrien S J; Karaca, Ezgi; Schmitz, Christophe; van Dijk, Marc; Bonvin, Alexandre M J J; Eisenstein, Miriam; Jiménez-García, Brian; Grosdidier, Solène; Solernou, Albert; Pérez-Cano, Laura; Pallara, Chiara; Fernández-Recio, Juan; Xu, Jianqing; Muthu, Pravin; Praneeth Kilambi, Krishna; Gray, Jeffrey J; Grudinin, Sergei; Derevyanko, Georgy; Mitchell, Julie C.; Wieting, John; Kanamori, Eiji; Tsuchiya, Yuko; Murakami, Yoichi; Sarmiento, Joy; Standley, Daron M.; Shirota, Matsuyuki; Kinoshita, Kengo; Nakamura, Haruki; Chavent, Matthieu; Ritchie, David W.; Park, Hahnbeom; Ko, Junsu; Lee, Hasup; Seok, Chaok; Shen, Yang; Kozakov, Dima; Vajda, Sandor; Kundrotas, Petras J.; Vakser, Ilya A.; Pierce, Brian G.; Hwang, Howook; Vreven, Thom; Weng, Zhiping; Buch, Idit; Farkash, Efrat; Wolfson, Haim J.; Zacharias, Martin; Qin, Sanbo; Zhou, Huan Xiang; Huang, Shen You; Zou, Xiaoqin; Wojdyla, Justyna A.; Kleanthous, Colin; Wodak, Shoshana J.

In: Proteins, Vol. 82, No. 4, 2014, p. 620-632.

Research output: Contribution to journalArticle

Lensink, MF, Moal, IH, Bates, PA, Kastritis, PL, Melquiond, ASJ, Karaca, E, Schmitz, C, van Dijk, M, Bonvin, AMJJ, Eisenstein, M, Jiménez-García, B, Grosdidier, S, Solernou, A, Pérez-Cano, L, Pallara, C, Fernández-Recio, J, Xu, J, Muthu, P, Praneeth Kilambi, K, Gray, JJ, Grudinin, S, Derevyanko, G, Mitchell, JC, Wieting, J, Kanamori, E, Tsuchiya, Y, Murakami, Y, Sarmiento, J, Standley, DM, Shirota, M, Kinoshita, K, Nakamura, H, Chavent, M, Ritchie, DW, Park, H, Ko, J, Lee, H, Seok, C, Shen, Y, Kozakov, D, Vajda, S, Kundrotas, PJ, Vakser, IA, Pierce, BG, Hwang, H, Vreven, T, Weng, Z, Buch, I, Farkash, E, Wolfson, HJ, Zacharias, M, Qin, S, Zhou, HX, Huang, SY, Zou, X, Wojdyla, JA, Kleanthous, C & Wodak, SJ 2014, 'Blind prediction of interfacial water positions in CAPRI', Proteins, vol. 82, no. 4, pp. 620-632. https://doi.org/10.1002/prot.24439
Lensink MF, Moal IH, Bates PA, Kastritis PL, Melquiond ASJ, Karaca E et al. Blind prediction of interfacial water positions in CAPRI. Proteins. 2014;82(4):620-632. https://doi.org/10.1002/prot.24439
Lensink, Marc F. ; Moal, Iain H. ; Bates, Paul A. ; Kastritis, Panagiotis L. ; Melquiond, Adrien S J ; Karaca, Ezgi ; Schmitz, Christophe ; van Dijk, Marc ; Bonvin, Alexandre M J J ; Eisenstein, Miriam ; Jiménez-García, Brian ; Grosdidier, Solène ; Solernou, Albert ; Pérez-Cano, Laura ; Pallara, Chiara ; Fernández-Recio, Juan ; Xu, Jianqing ; Muthu, Pravin ; Praneeth Kilambi, Krishna ; Gray, Jeffrey J ; Grudinin, Sergei ; Derevyanko, Georgy ; Mitchell, Julie C. ; Wieting, John ; Kanamori, Eiji ; Tsuchiya, Yuko ; Murakami, Yoichi ; Sarmiento, Joy ; Standley, Daron M. ; Shirota, Matsuyuki ; Kinoshita, Kengo ; Nakamura, Haruki ; Chavent, Matthieu ; Ritchie, David W. ; Park, Hahnbeom ; Ko, Junsu ; Lee, Hasup ; Seok, Chaok ; Shen, Yang ; Kozakov, Dima ; Vajda, Sandor ; Kundrotas, Petras J. ; Vakser, Ilya A. ; Pierce, Brian G. ; Hwang, Howook ; Vreven, Thom ; Weng, Zhiping ; Buch, Idit ; Farkash, Efrat ; Wolfson, Haim J. ; Zacharias, Martin ; Qin, Sanbo ; Zhou, Huan Xiang ; Huang, Shen You ; Zou, Xiaoqin ; Wojdyla, Justyna A. ; Kleanthous, Colin ; Wodak, Shoshana J. / Blind prediction of interfacial water positions in CAPRI. In: Proteins. 2014 ; Vol. 82, No. 4. pp. 620-632.
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T1 - Blind prediction of interfacial water positions in CAPRI

AU - Lensink, Marc F.

AU - Moal, Iain H.

AU - Bates, Paul A.

AU - Kastritis, Panagiotis L.

AU - Melquiond, Adrien S J

AU - Karaca, Ezgi

AU - Schmitz, Christophe

AU - van Dijk, Marc

AU - Bonvin, Alexandre M J J

AU - Eisenstein, Miriam

AU - Jiménez-García, Brian

AU - Grosdidier, Solène

AU - Solernou, Albert

AU - Pérez-Cano, Laura

AU - Pallara, Chiara

AU - Fernández-Recio, Juan

AU - Xu, Jianqing

AU - Muthu, Pravin

AU - Praneeth Kilambi, Krishna

AU - Gray, Jeffrey J

AU - Grudinin, Sergei

AU - Derevyanko, Georgy

AU - Mitchell, Julie C.

AU - Wieting, John

AU - Kanamori, Eiji

AU - Tsuchiya, Yuko

AU - Murakami, Yoichi

AU - Sarmiento, Joy

AU - Standley, Daron M.

AU - Shirota, Matsuyuki

AU - Kinoshita, Kengo

AU - Nakamura, Haruki

AU - Chavent, Matthieu

AU - Ritchie, David W.

AU - Park, Hahnbeom

AU - Ko, Junsu

AU - Lee, Hasup

AU - Seok, Chaok

AU - Shen, Yang

AU - Kozakov, Dima

AU - Vajda, Sandor

AU - Kundrotas, Petras J.

AU - Vakser, Ilya A.

AU - Pierce, Brian G.

AU - Hwang, Howook

AU - Vreven, Thom

AU - Weng, Zhiping

AU - Buch, Idit

AU - Farkash, Efrat

AU - Wolfson, Haim J.

AU - Zacharias, Martin

AU - Qin, Sanbo

AU - Zhou, Huan Xiang

AU - Huang, Shen You

AU - Zou, Xiaoqin

AU - Wojdyla, Justyna A.

AU - Kleanthous, Colin

AU - Wodak, Shoshana J.

PY - 2014

Y1 - 2014

N2 - We report the first assessment of blind predictions of water positions at protein-protein interfaces, performed as part of the critical assessment of predicted interactions (CAPRI) community-wide experiment. Groups submitting docking predictions for the complex of the DNase domain of colicin E2 and Im2 immunity protein (CAPRI Target 47), were invited to predict the positions of interfacial water molecules using the method of their choice. The predictions-20 groups submitted a total of 195 models-were assessed by measuring the recall fraction of water-mediated protein contacts. Of the 176 high- or medium-quality docking models-a very good docking performance per se-only 44% had a recall fraction above 0.3, and a mere 6% above 0.5. The actual water positions were in general predicted to an accuracy level no better than 1.5 Å, and even in good models about half of the contacts represented false positives. This notwithstanding, three hotspot interface water positions were quite well predicted, and so was one of the water positions that is believed to stabilize the loop that confers specificity in these complexes. Overall the best interface water predictions was achieved by groups that also produced high-quality docking models, indicating that accurate modelling of the protein portion is a determinant factor. The use of established molecular mechanics force fields, coupled to sampling and optimization procedures also seemed to confer an advantage. Insights gained from this analysis should help improve the prediction of protein-water interactions and their role in stabilizing protein complexes.

AB - We report the first assessment of blind predictions of water positions at protein-protein interfaces, performed as part of the critical assessment of predicted interactions (CAPRI) community-wide experiment. Groups submitting docking predictions for the complex of the DNase domain of colicin E2 and Im2 immunity protein (CAPRI Target 47), were invited to predict the positions of interfacial water molecules using the method of their choice. The predictions-20 groups submitted a total of 195 models-were assessed by measuring the recall fraction of water-mediated protein contacts. Of the 176 high- or medium-quality docking models-a very good docking performance per se-only 44% had a recall fraction above 0.3, and a mere 6% above 0.5. The actual water positions were in general predicted to an accuracy level no better than 1.5 Å, and even in good models about half of the contacts represented false positives. This notwithstanding, three hotspot interface water positions were quite well predicted, and so was one of the water positions that is believed to stabilize the loop that confers specificity in these complexes. Overall the best interface water predictions was achieved by groups that also produced high-quality docking models, indicating that accurate modelling of the protein portion is a determinant factor. The use of established molecular mechanics force fields, coupled to sampling and optimization procedures also seemed to confer an advantage. Insights gained from this analysis should help improve the prediction of protein-water interactions and their role in stabilizing protein complexes.

KW - Blind prediction

KW - CAPRI

KW - Protein docking

KW - Protein interface

KW - Water

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