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PMID: 22253587 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Kinetic rate constant prediction supports the conformational selection mechanism of protein binding.

PLoS computational biology ·Vol. 8 ·No. 1 ·2012-01-00 ·Pages e1002351

Moal IH, Bates PA

Abstract

The prediction of protein-protein kinetic rate constants provides a fundamental test of our understanding of molecular recognition, and will play an important role in the modeling of complex biological systems. In this paper, a feature selection and regression algorithm is applied to mine a large set of molecular descriptors and construct simple models for association and dissociation rate constants using empirical data. Using separate test data for validation, the predicted rate constants can be combined to calculate binding affinity with accuracy matching that of state of the art empirical free energy functions. The models show that the rate of association is linearly related to the proportion of unbound proteins in the bound conformational ensemble relative to the unbound conformational ensemble, indicating that the binding partners must adopt a geometry near to that of the bound prior to binding. Mirroring the conformational selection and population shift mechanism of protein binding, the models provide a strong separate line of evidence for the preponderance of this mechanism in protein-protein binding, complementing structural and theoretical studies.

MeSH Terms
Algorithms Binding Sites Kinetics Models, Molecular Protein Conformation Proteins/chemistry,metabolism Thermodynamics
Chemicals
Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Moal Iain H
Protein Interactions and Docking Laboratory, Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Spain. imoal@bsc.es
Bates Paul A
References (60)
60 references, click to expand
  1. Antibody multispecificity mediated by conformational diversity.
    Science. 2003 Feb 28;299(5611):1362-7 PMID: 12610298
  2. New measures for estimating surface complementarity and packing at protein-protein interfaces.
    FEBS Lett. 2010 Mar 19;584(6):1163-8 PMID: 20153323
  3. Energy functions that discriminate X-ray and near native folds from well-constructed decoys.
    J Mol Biol. 1996 May 3;258(2):367-92 PMID: 8627632
  4. Fasciculin 2 binds to the peripheral site on acetylcholinesterase and inhibits substrate hydrolysis by slowing a step involving proton transfer during enzyme acylation.
    J Biol Chem. 1995 Aug 25;270(34):19694-701 PMID: 7649979
  5. Folding funnels and binding mechanisms.
    Protein Eng. 1999 Sep;12(9):713-20 PMID: 10506280
  6. Structural systems biology: modelling protein interactions.
    Nat Rev Mol Cell Biol. 2006 Mar;7(3):188-97 PMID: 16496021
  7. From induced fit to conformational selection: a continuum of binding mechanism controlled by the timescale of conformational transitions.
    Biophys J. 2010 Mar 17;98(6):L15-7 PMID: 20303846
  8. ProtorP: a protein-protein interaction analysis server.
    Bioinformatics. 2009 Feb 1;25(3):413-4 PMID: 19001476
  9. Effective energy function for proteins in solution.
    Proteins. 1999 May 1;35(2):133-52 PMID: 10223287
  10. Do we underestimate the importance of water in cell biology?
    Nat Rev Mol Cell Biol. 2006 Nov;7(11):861-6 PMID: 16955076
  11. Lack of significant differences in association rates and affinities of antibodies from short-term and long-term responses to hen egg lysozyme.
    J Immunol. 1999 May 15;162(10):6040-5 PMID: 10229844
  12. Prediction of protein conformational freedom from distance constraints.
    Proteins. 1997 Oct;29(2):240-51 PMID: 9329088
  13. Dynamic energy landscape view of coupled binding and protein conformational change: induced-fit versus population-shift mechanisms.
    Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11182-7 PMID: 18678900
  14. Protein fragment reconstruction using various modeling techniques.
    J Comput Aided Mol Des. 2003 Nov;17(11):725-38 PMID: 15072433
  15. Fundamental aspects of protein-protein association kinetics.
    Chem Rev. 2009 Mar 11;109(3):839-60 PMID: 19196002
  16. Folding funnels, binding funnels, and protein function.
    Protein Sci. 1999 Jun;8(6):1181-90 PMID: 10386868
  17. Targeting the human cancer pathway protein interaction network by structural genomics.
    Mol Cell Proteomics. 2008 Oct;7(10):2048-60 PMID: 18487680
  18. Quantitative prediction of protein-protein binding affinity with a potential of mean force considering volume correction.
    Protein Sci. 2009 Dec;18(12):2550-8 PMID: 19798743
  19. Spectroscopic, calorimetric, and kinetic demonstration of conformational adaptation in peptide-antibody recognition.
    Biochemistry. 1995 Dec 19;34(50):16509-18 PMID: 8845380
  20. Water and proteins: a love-hate relationship.
    Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3325-6 PMID: 14993602
  21. Bridging from molecular simulation to biochemical networks.
    Curr Opin Struct Biol. 2007 Apr;17(2):166-72 PMID: 17395455
  22. The role of dynamic conformational ensembles in biomolecular recognition.
    Nat Chem Biol. 2009 Nov;5(11):789-96 PMID: 19841628
  23. Analyzing protein interaction networks using structural information.
    Annu Rev Biochem. 2008;77:415-41 PMID: 18304007
  24. Residue-residue potentials with a favorable contact pair term and an unfavorable high packing density term, for simulation and threading.
    J Mol Biol. 1996 Mar 1;256(3):623-44 PMID: 8604144
  25. Three-dimensional modeling of protein interactions and complexes is going 'omics.
    Curr Opin Struct Biol. 2011 Apr;21(2):200-8 PMID: 21320770
  26. Fast predictions of thermodynamics and kinetics of protein-protein recognition from structures: from molecular design to systems biology.
    Mol Biosyst. 2009 Apr;5(4):323-34 PMID: 19396368
  27. PyRosetta: a script-based interface for implementing molecular modeling algorithms using Rosetta.
    Bioinformatics. 2010 Mar 1;26(5):689-91 PMID: 20061306
  28. OPUS-Ca: a knowledge-based potential function requiring only Calpha positions.
    Protein Sci. 2007 Jul;16(7):1449-63 PMID: 17586777
  29. A physical reference state unifies the structure-derived potential of mean force for protein folding and binding.
    Proteins. 2004 Jul 1;56(1):93-101 PMID: 15162489
  30. CHARMM: the biomolecular simulation program.
    J Comput Chem. 2009 Jul 30;30(10):1545-614 PMID: 19444816
  31. Protein-protein binding affinity prediction on a diverse set of structures.
    Bioinformatics. 2011 Nov 1;27(21):3002-9 PMID: 21903632
  32. Application of a Theory of Enzyme Specificity to Protein Synthesis.
    Proc Natl Acad Sci U S A. 1958 Feb;44(2):98-104 PMID: 16590179
  33. Mathematical modeling identifies Smad nucleocytoplasmic shuttling as a dynamic signal-interpreting system.
    Proc Natl Acad Sci U S A. 2008 May 6;105(18):6608-13 PMID: 18443295
  34. A structure-based benchmark for protein-protein binding affinity.
    Protein Sci. 2011 Mar;20(3):482-91 PMID: 21213247
  35. Antigen recognition by conformational selection.
    FEBS Lett. 1999 Apr 30;450(1-2):149-53 PMID: 10350075
  36. Distance-scaled, finite ideal-gas reference state improves structure-derived potentials of mean force for structure selection and stability prediction.
    Protein Sci. 2002 Nov;11(11):2714-26 PMID: 12381853
  37. Kinetic analysis of macromolecular interactions using surface plasmon resonance biosensors.
    Methods Enzymol. 1998;295:268-94 PMID: 9750223
  38. Biomolecular diffusional association.
    Curr Opin Struct Biol. 2002 Apr;12(2):204-13 PMID: 11959498
  39. Binding of 125I-fasciculin to rat brain acetylcholinesterase. The complex still binds diisopropyl fluorophosphate.
    J Biol Chem. 1993 Jun 15;268(17):12458-67 PMID: 8509385
  40. Transition networks for modeling the kinetics of conformational change in macromolecules.
    Curr Opin Struct Biol. 2008 Apr;18(2):154-62 PMID: 18378442
  41. Adhesive water networks facilitate binding of protein interfaces.
    Nat Commun. 2011 Mar 29;2:261 PMID: 21448160
  42. Conformational isomerism and the diversity of antibodies.
    Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10370-4 PMID: 7937957
  43. Protein folding mediated by solvation: water expulsion and formation of the hydrophobic core occur after the structural collapse.
    Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):685-90 PMID: 11805324
  44. Selected-fit versus induced-fit protein binding: kinetic differences and mutational analysis.
    Proteins. 2009 Apr;75(1):104-10 PMID: 18798570
  45. A systematic study of the energetics involved in structural changes upon association and connectivity in protein interaction networks.
    Structure. 2011 Jun 8;19(6):881-9 PMID: 21645858
  46. Specific interactions for ab initio folding of protein terminal regions with secondary structures.
    Proteins. 2008 Aug;72(2):793-803 PMID: 18260109
  47. Evaluation of a fast implicit solvent model for molecular dynamics simulations.
    Proteins. 2002 Jan 1;46(1):24-33 PMID: 11746700
  48. Structures in systems biology.
    Curr Opin Struct Biol. 2007 Jun;17(3):378-84 PMID: 17574836
  49. Pushing structural information into the yeast interactome by high-throughput protein docking experiments.
    PLoS Comput Biol. 2009 Aug;5(8):e1000490 PMID: 19714207
  50. Predicting kinetic constants of protein-protein interactions based on structural properties.
    Proteins. 2011 Mar;79(3):720-34 PMID: 21287608
  51. Refined models for computer simulation of protein folding. Applications to the study of conserved secondary structure and flexible hinge points during the folding of pancreatic trypsin inhibitor.
    J Mol Biol. 1979 Jul 25;132(1):19-51 PMID: 513136
  52. OPUS-PSP: an orientation-dependent statistical all-atom potential derived from side-chain packing.
    J Mol Biol. 2008 Feb 8;376(1):288-301 PMID: 18177896
  53. Potentials 'R' Us web-server for protein energy estimations with coarse-grained knowledge-based potentials.
    BMC Bioinformatics. 2010 Feb 17;11:92 PMID: 20163737
  54. Water in protein structure prediction.
    Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3352-7 PMID: 14988499
  55. Four-body contact potentials derived from two protein datasets to discriminate native structures from decoys.
    Proteins. 2007 Jul 1;68(1):57-66 PMID: 17393455
  56. A systematic study of low-resolution recognition in protein--protein complexes.
    Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8477-82 PMID: 10411900
  57. FireDock: fast interaction refinement in molecular docking.
    Proteins. 2007 Oct 1;69(1):139-59 PMID: 17598144
  58. Induced fit, conformational selection and independent dynamic segments: an extended view of binding events.
    Trends Biochem Sci. 2010 Oct;35(10):539-46 PMID: 20541943
  59. Assembly and function of a quaternary signal transduction complex monitored by surface plasmon resonance.
    Nature. 1993 Sep 23;365(6444):343-7 PMID: 8377825
  60. Structure-based thermodynamic analysis of the dissociation of protein phosphatase-1 catalytic subunit and microcystin-LR docked complexes.
    Protein Sci. 2000 Feb;9(2):252-64 PMID: 10716177
Article Info
Journal
PLoS computational biology
Abbr.
PLoS Comput Biol
ISSN
1553-7358
DOI
10.1371/journal.pcbi.1002351
Email
imoal@bsc.es
Published
2012-01-00
Epub
2012-00-12
Pages
e1002351
Language
English
Region
United States
NLM ID
101238922
PMCID
PMC3257286
Subset
IM
Grants
Cancer Research UK · United Kingdom
External Links
PubMed source DOI: 10.1371/journal.pcbi.1002351 PMC Full Text View journal details
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