Extending RosettaDock with water, sugar, and pH for prediction of complex structures and affinities for CAPRI rounds 20-27

Krishna Praneeth Kilambi, Michael S. Pacella, Jianqing Xu, Jason W. Labonte, Justin R. Porter, Pravin Muthu, Kevin Drew, Daisuke Kuroda, Ora Schueler-Furman, Richard Bonneau, Jeffrey J. Gray

Research output: Contribution to journalArticle

Abstract

Rounds 20-27 of the Critical Assessment of PRotein Interactions (CAPRI) provided a testing platform for computational methods designed to address a wide range of challenges. The diverse targets drove the creation of and new combinations of computational tools. In this study, RosettaDock and other novel Rosetta protocols were used to successfully predict four of the 10 blind targets. For example, for DNase domain of Colicin E2-Im2 immunity protein, RosettaDock and RosettaLigand were used to predict the positions of water molecules at the interface, recovering 46% of the native water-mediated contacts. For α-repeat Rep4-Rep2 and g-type lysozyme-PliG inhibitor complexes, homology models were built and standard and pH-sensitive docking algorithms were used to generate structures with interface RMSD values of 3.3 Å and 2.0 Å, respectively. A novel flexible sugar-protein docking protocol was also developed and used for structure prediction of the BT4661-heparin-like saccharide complex, recovering 71% of the native contacts. Challenges remain in the generation of accurate homology models for protein mutants and sampling during global docking. On proteins designed to bind influenza hemagglutinin, only about half of the mutations were identified that affect binding (T55: 54%; T56: 48%). The prediction of the structure of the xylanase complex involving homology modeling and multidomain docking pushed the limits of global conformational sampling and did not result in any successful prediction. The diversity of problems at hand requires computational algorithms to be versatile; the recent additions to the Rosetta suite expand the capabilities to encompass more biologically realistic docking problems.

Original languageEnglish (US)
Pages (from-to)2201-2209
Number of pages9
JournalProteins: Structure, Function and Genetics
Volume81
Issue number12
DOIs
StatePublished - Dec 2013

Fingerprint

Sugars
Water
Proteins
Colicins
Deoxyribonucleases
Sampling
Hemagglutinins
Mutant Proteins
Muramidase
Human Influenza
Heparin
Immunity
Computational methods
Hand
Mutation
Molecules
Testing

Keywords

  • Binding
  • CAPRI
  • Protein docking
  • Protein interactions

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Molecular Biology

Cite this

Extending RosettaDock with water, sugar, and pH for prediction of complex structures and affinities for CAPRI rounds 20-27. / Kilambi, Krishna Praneeth; Pacella, Michael S.; Xu, Jianqing; Labonte, Jason W.; Porter, Justin R.; Muthu, Pravin; Drew, Kevin; Kuroda, Daisuke; Schueler-Furman, Ora; Bonneau, Richard; Gray, Jeffrey J.

In: Proteins: Structure, Function and Genetics, Vol. 81, No. 12, 12.2013, p. 2201-2209.

Research output: Contribution to journalArticle

Kilambi, KP, Pacella, MS, Xu, J, Labonte, JW, Porter, JR, Muthu, P, Drew, K, Kuroda, D, Schueler-Furman, O, Bonneau, R & Gray, JJ 2013, 'Extending RosettaDock with water, sugar, and pH for prediction of complex structures and affinities for CAPRI rounds 20-27', Proteins: Structure, Function and Genetics, vol. 81, no. 12, pp. 2201-2209. https://doi.org/10.1002/prot.24425
Kilambi, Krishna Praneeth ; Pacella, Michael S. ; Xu, Jianqing ; Labonte, Jason W. ; Porter, Justin R. ; Muthu, Pravin ; Drew, Kevin ; Kuroda, Daisuke ; Schueler-Furman, Ora ; Bonneau, Richard ; Gray, Jeffrey J. / Extending RosettaDock with water, sugar, and pH for prediction of complex structures and affinities for CAPRI rounds 20-27. In: Proteins: Structure, Function and Genetics. 2013 ; Vol. 81, No. 12. pp. 2201-2209.
@article{78848723901648719786b99b4ea664a1,
title = "Extending RosettaDock with water, sugar, and pH for prediction of complex structures and affinities for CAPRI rounds 20-27",
abstract = "Rounds 20-27 of the Critical Assessment of PRotein Interactions (CAPRI) provided a testing platform for computational methods designed to address a wide range of challenges. The diverse targets drove the creation of and new combinations of computational tools. In this study, RosettaDock and other novel Rosetta protocols were used to successfully predict four of the 10 blind targets. For example, for DNase domain of Colicin E2-Im2 immunity protein, RosettaDock and RosettaLigand were used to predict the positions of water molecules at the interface, recovering 46{\%} of the native water-mediated contacts. For α-repeat Rep4-Rep2 and g-type lysozyme-PliG inhibitor complexes, homology models were built and standard and pH-sensitive docking algorithms were used to generate structures with interface RMSD values of 3.3 {\AA} and 2.0 {\AA}, respectively. A novel flexible sugar-protein docking protocol was also developed and used for structure prediction of the BT4661-heparin-like saccharide complex, recovering 71{\%} of the native contacts. Challenges remain in the generation of accurate homology models for protein mutants and sampling during global docking. On proteins designed to bind influenza hemagglutinin, only about half of the mutations were identified that affect binding (T55: 54{\%}; T56: 48{\%}). The prediction of the structure of the xylanase complex involving homology modeling and multidomain docking pushed the limits of global conformational sampling and did not result in any successful prediction. The diversity of problems at hand requires computational algorithms to be versatile; the recent additions to the Rosetta suite expand the capabilities to encompass more biologically realistic docking problems.",
keywords = "Binding, CAPRI, Protein docking, Protein interactions",
author = "Kilambi, {Krishna Praneeth} and Pacella, {Michael S.} and Jianqing Xu and Labonte, {Jason W.} and Porter, {Justin R.} and Pravin Muthu and Kevin Drew and Daisuke Kuroda and Ora Schueler-Furman and Richard Bonneau and Gray, {Jeffrey J.}",
year = "2013",
month = "12",
doi = "10.1002/prot.24425",
language = "English (US)",
volume = "81",
pages = "2201--2209",
journal = "Proteins: Structure, Function and Genetics",
issn = "0887-3585",
publisher = "Wiley-Liss Inc.",
number = "12",

}

TY - JOUR

T1 - Extending RosettaDock with water, sugar, and pH for prediction of complex structures and affinities for CAPRI rounds 20-27

AU - Kilambi, Krishna Praneeth

AU - Pacella, Michael S.

AU - Xu, Jianqing

AU - Labonte, Jason W.

AU - Porter, Justin R.

AU - Muthu, Pravin

AU - Drew, Kevin

AU - Kuroda, Daisuke

AU - Schueler-Furman, Ora

AU - Bonneau, Richard

AU - Gray, Jeffrey J.

PY - 2013/12

Y1 - 2013/12

N2 - Rounds 20-27 of the Critical Assessment of PRotein Interactions (CAPRI) provided a testing platform for computational methods designed to address a wide range of challenges. The diverse targets drove the creation of and new combinations of computational tools. In this study, RosettaDock and other novel Rosetta protocols were used to successfully predict four of the 10 blind targets. For example, for DNase domain of Colicin E2-Im2 immunity protein, RosettaDock and RosettaLigand were used to predict the positions of water molecules at the interface, recovering 46% of the native water-mediated contacts. For α-repeat Rep4-Rep2 and g-type lysozyme-PliG inhibitor complexes, homology models were built and standard and pH-sensitive docking algorithms were used to generate structures with interface RMSD values of 3.3 Å and 2.0 Å, respectively. A novel flexible sugar-protein docking protocol was also developed and used for structure prediction of the BT4661-heparin-like saccharide complex, recovering 71% of the native contacts. Challenges remain in the generation of accurate homology models for protein mutants and sampling during global docking. On proteins designed to bind influenza hemagglutinin, only about half of the mutations were identified that affect binding (T55: 54%; T56: 48%). The prediction of the structure of the xylanase complex involving homology modeling and multidomain docking pushed the limits of global conformational sampling and did not result in any successful prediction. The diversity of problems at hand requires computational algorithms to be versatile; the recent additions to the Rosetta suite expand the capabilities to encompass more biologically realistic docking problems.

AB - Rounds 20-27 of the Critical Assessment of PRotein Interactions (CAPRI) provided a testing platform for computational methods designed to address a wide range of challenges. The diverse targets drove the creation of and new combinations of computational tools. In this study, RosettaDock and other novel Rosetta protocols were used to successfully predict four of the 10 blind targets. For example, for DNase domain of Colicin E2-Im2 immunity protein, RosettaDock and RosettaLigand were used to predict the positions of water molecules at the interface, recovering 46% of the native water-mediated contacts. For α-repeat Rep4-Rep2 and g-type lysozyme-PliG inhibitor complexes, homology models were built and standard and pH-sensitive docking algorithms were used to generate structures with interface RMSD values of 3.3 Å and 2.0 Å, respectively. A novel flexible sugar-protein docking protocol was also developed and used for structure prediction of the BT4661-heparin-like saccharide complex, recovering 71% of the native contacts. Challenges remain in the generation of accurate homology models for protein mutants and sampling during global docking. On proteins designed to bind influenza hemagglutinin, only about half of the mutations were identified that affect binding (T55: 54%; T56: 48%). The prediction of the structure of the xylanase complex involving homology modeling and multidomain docking pushed the limits of global conformational sampling and did not result in any successful prediction. The diversity of problems at hand requires computational algorithms to be versatile; the recent additions to the Rosetta suite expand the capabilities to encompass more biologically realistic docking problems.

KW - Binding

KW - CAPRI

KW - Protein docking

KW - Protein interactions

UR - http://www.scopus.com/inward/record.url?scp=84888308467&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888308467&partnerID=8YFLogxK

U2 - 10.1002/prot.24425

DO - 10.1002/prot.24425

M3 - Article

C2 - 24123494

AN - SCOPUS:84888308467

VL - 81

SP - 2201

EP - 2209

JO - Proteins: Structure, Function and Genetics

JF - Proteins: Structure, Function and Genetics

SN - 0887-3585

IS - 12

ER -