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Conformation and dynamics of 8-Arg-vasopressin in solution

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Abstract

Arginine-vasopressin was subjected to a long (11 μs) molecular dynamics simulation in aqueous solution. Analysis of the results by DASH and principal components analyses revealed four main ring conformations that move essentially independently of the faster-moving tail region. Two of these conformations (labeled “saddle”) feature well-defined β-turns in the ring and conserved transannular hydrogen bonds, whereas the other two (“open”) feature neither. The conformations have been identified and defined and are all of sufficient stability to be considered candidates for biological conformations in their cognate receptors.

An illustration of the ring alignment of the backbone cartoons of the four main ring states of 8-Arg-vasopressin (T10_8,1,4,6) including the tail

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References

  1. du Vigneaud V, Gish DT, Katsoyannis PG (1954) A Synthetic Preparation Possessing Biological Properties Associated with Arginine Vasopressin. J Am Chem Soc 76:4751–4752

    Article  Google Scholar 

  2. Laycock JF (2010) Perspectives on vasopressin. Imperial College Press, London

    Google Scholar 

  3. Gimpl G, Fahrenholz F (2001) The oxytocin receptor system: structure, function, and regulation. Physiol Rev 81:629–683

    CAS  Google Scholar 

  4. Strand FL (1999) Neuropeptides: regulators of physiological processes. MIT Press, Cambridge, pp 229–265

    Google Scholar 

  5. Barberis C, Morin D, Durroux T, Mouillac B, Guillon G, Seyer R, Hibert M, Tribollet E, Manning M (1999) Molecular pharmacology of AVP and OT receptors and therapeutic potential. Drug News Perspect 12:279–292

    Article  CAS  Google Scholar 

  6. Wu CK, Hu B, Rose JP, Liu ZJ, Nguyen TL, Zheng C, Breslow E, Wang BC (2001) Structures of an unliganded neurophysin and its vasopressin complex: implications for binding and allosteric mechanisms. Protein Sci: Publ Protein Soc 10:1869–1880

    Article  CAS  Google Scholar 

  7. Fujiwara Y, Tanoue A, Tsujimoto G, Koshimizu TA (2012) The roles of V1a vasopressin receptors in blood pressure homeostasis: a review of studies on V1a receptor knockout mice. Clin Exp Nephrol 16:30–34

    Article  CAS  Google Scholar 

  8. Pittman QJ, Bagdan B (1992) Vasopressin involvement in central control of blood pressure. Prog Brain Res 91:69–74

    Article  CAS  Google Scholar 

  9. Pittman QJ, Wilkinson MF (1992) Central arginine vasopressin and endogenous antipyresis. Can J Physiol Pharmacol 70:786–790

    Article  CAS  Google Scholar 

  10. Mogil JS, Sorge RE, LaCroix-Fralish ML et al (2011) Pain sensitivity and vasopressin analgesia are mediated by a gene-sex-environment interaction. Nat Neurosci 14:1569–1573

    Article  CAS  Google Scholar 

  11. Manning M, Misicka A, Olma A et al (2012) Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics. J Neuroendocrinol 24:609–628

    Article  CAS  Google Scholar 

  12. Jard S (1998) Vasopressin receptors. A historical survey. Adv Exp Med Biol 449:1–13

    Article  CAS  Google Scholar 

  13. Dunning BE, Moltz JH, Fawcett CP (1984) Modulation of insulin and glucagon secretion from the perfused rat pancreas by the neurohypophysial hormones and by desamino-D-arginine vasopressin (DDAVP). Peptides 5:871–875

    Article  CAS  Google Scholar 

  14. Young LJ, Flanagan-Cato LM (2012) Editorial comment: oxytocin, vasopressin and social behavior. Horm Behav 61:227–229

    Article  Google Scholar 

  15. Insel TR, O'Brien DJ, Leckman JF (1999) Oxytocin, vasopressin, and autism: is there a connection? Biol Psychiatry 45:145–157

    Article  CAS  Google Scholar 

  16. Yamaguchi Y, Suzuki T, Mizoro Y, Kori H, Okada K et al (2013) Mice genetically deficient in vasopressin V1a and V1b receptors are resistant to jet lag. Science 342:85–90

    Article  CAS  Google Scholar 

  17. Manning M, Chan WY, Sawyer WH (1993) Design of cyclic and linear peptide antagonists of vasopressin and oxytocin: current status and future directions. Regul Pept 45:279–283

    Article  CAS  Google Scholar 

  18. Verbalis JG (2003) Disorders of body water homeostasis. Best Practice Res Clin Endocrinol Metab 17:471–503

    Article  CAS  Google Scholar 

  19. Lehrich RW, Greenberg A (2012) Hyponatremia and the use of vasopressin receptor antagonists in critically ill patients. J Intensive Care Med 27:207–218

    Article  Google Scholar 

  20. Verbalis JG (2006) AVP receptor antagonists as aquaretics: review and assessment of clinical data. Cleve Clin J Med 73(Suppl 3):S24–S33

    Article  Google Scholar 

  21. Barlow M (2002) Vasopressin. Emerg Med (Freemantle) 14:304–314

    Article  Google Scholar 

  22. Syed Ibrahim B, Pattabhi V (2005) Trypsin inhibition by a peptide hormone: crystal structure of trypsin-vasopressin complex. J Mol Biol 348:1191–1198

    Article  CAS  Google Scholar 

  23. Rose JP, Wu CK, Hsiao CD, Breslow E, Wang BC (1996) Crystal structure of the neurophysin-oxytocin complex. Nat Struct Biol 3:163–169

    Article  CAS  Google Scholar 

  24. Schmidt JM, Ohlenschlager O, Ruterjans H et al (1991) Conformation of [8-arginine]vasopressin and V1 antagonists in dimethyl sulfoxide solution derived from two-dimensional NMR spectroscopy and molecular dynamics simulation. Eur J Biochem 201:355–371

    Article  CAS  Google Scholar 

  25. Sikorska E, Rodziewicz-Motowidlo S (2008) Conformational studies of vasopressin and mesotocin using NMR spectroscopy and molecular modelling methods. Part I: Studies in water. J Pept Sci 14:76–84

    Article  CAS  Google Scholar 

  26. Rodziewicz-Motowidlo S, Sikorska E, Oleszczuk M, Czaplewski C (2008) Conformational studies of vasopressin and mesotocin using NMR spectroscopy and molecular modelling methods. Part II: Studies in the SDS micelle. J Pept Sci 14:85–96

    Article  CAS  Google Scholar 

  27. Liwo A, Tempczyk A, Oldziej S et al (1996) Exploration of the conformational space of oxytocin and arginine-vasopressin using the electrostatically driven Monte Carlo and molecular dynamics methods. Biopolymers 38:157–175

    Article  CAS  Google Scholar 

  28. Czaplewski C, Kazmierkiewicz R, Ciarkowski J (1998) Molecular modeling of the human vasopressin V2 receptor/agonist complex. J Comput Aided Mol Des 12:275–287

    Article  CAS  Google Scholar 

  29. Mouillac B, Chini B, Balestre MN et al (1995) The binding site of neuropeptide vasopressin V1a receptor. Evidence for a major localization within transmembrane regions. J Biol Chem 270:25771–25777

    Article  CAS  Google Scholar 

  30. Barberis C, Mouillac B, Durroux T (1998) Structural bases of vasopressin/oxytocin receptor function. J Endocrinol 156(2):223–229

    Article  CAS  Google Scholar 

  31. Schwyzer R (1995) In search of the ‘bio-active conformation’—is it induced by the target cell membrane? J Mol Recognit 8:3–8

    Article  CAS  Google Scholar 

  32. Mierke DF, Giragossian C (2001) Peptide hormone binding to G-protein-coupled receptors: structural characterization via NMR techniques. Med Res Rev 21:450–471

    Article  CAS  Google Scholar 

  33. Changeux JP, Edelstein SJ (2005) Allosteric mechanisms of signal transduction. Science 308:1424–1428

    Article  CAS  Google Scholar 

  34. Cui Q, Karplus M (2008) Allostery and cooperativity revisited. Protein Sci: Publ Protein Soc 17:1295–1307

    Article  CAS  Google Scholar 

  35. Gunasekaran K, Ma B, Nussinov R (2004) Is allostery an intrinsic property of all dynamic proteins? Proteins 57:433–443

    Article  CAS  Google Scholar 

  36. Shao J, Tanner SW, Thompson N, Cheatham TE (2007) Clustering Molecular Dynamics Trajectories: 1. Characterizing the Performance of Different Clustering Algorithms. J Chem Theory Comput 3:2312–2334

    Article  CAS  Google Scholar 

  37. Case DA, Darden TA, Cheatham II TE, et al (2008) AMBER 10. University of California, San Francisco

  38. Case DA, Darden TA, Cheatham II TE, et al (2008) AmberTools 1.0. University of California, San Francisco

  39. Salt DW, Hudson BD, Banting L et al (2005) DASH: a novel analysis method for molecular dynamics simulation data. Analysis of ligands of PPAR-gamma. J Med Chem 48:3214–3220

    Article  CAS  Google Scholar 

  40. Jorgensen WL, Chandrasekhar J, Madura JD et al (1983) Comparison of Simple Potential Functions for Simulating Liquid Water. J Chem Phys 79:926–935

    Article  CAS  Google Scholar 

  41. Horn HW, Swope WC, Pitera JW et al (2004) Development of an improved four-site water model for biomolecular simulations: TIP4P-Ew. J Chem Phys 120:9665–9678

    Article  CAS  Google Scholar 

  42. Hornak V, Abel R, Okur A et al (2006) Comparison of multiple amber force fields and development of improved protein backbone parameters. Proteins Struct Funct Bioinforma 65:712–725

    Article  CAS  Google Scholar 

  43. Berendsen HJC, Postma JPM, van Gunsteren WF et al (1984) Comparison of multiple amber force fields and development of improved protein backbone parameters. J Chem Phys 81:3684–3690

    Article  CAS  Google Scholar 

  44. Ryckaert JP, Ciccotti G, Berendsen HJC (1977) Numerical-Integration of Cartesian Equations of Motion of a System with Constraints - Molecular-Dynamics of N-Alkanes. J Comput Phys 23:327–341

    Article  CAS  Google Scholar 

  45. Darden T, York D, Pedersen L (1993) Particle mesh Ewald—an N.Log(N) method for Ewald sums in large systems. J Chem Phys 98:10089–10092

    Article  CAS  Google Scholar 

  46. DASH 1.0 (2008) Available from: http://www.port.ac.uk/research/cmd/software

  47. SAR-Caddle (2013) Cepos InSilico, Kempston, UK; Available from: http://www.ceposinsilico.de/products/sar-caddle.htm

  48. Kaiser HF (1960) The application of electronic computers to factor analysis. Educ Psychol Meas 20:141–151

    Article  Google Scholar 

  49. Pazderková M, Bednárová L, Dlouhá H et al (2012) Electronic and vibrational optical activity of several peptides related to neurohypophyseal hormones: disulfide group conformation. Biopolymers 97:923–932

    Article  Google Scholar 

  50. Venkatachalam CM (1968) Stereochemical criteria for polypeptides and proteins. V. Conformation of a system of three linked peptide units. Biopolymers 6:1425–1436

    Article  CAS  Google Scholar 

  51. Richardson JS (1981) The anatomy and taxonomy of protein structure. Adv Protein Chem 34:167–339

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the European project “Peptide Research Network of Excellence” PeReNE as part of the Interreg IVA France (Channel)—England 2007–2014 program (Interreg EU). We thank Jonathan Essex (University of Southampton, UK) and Ronan Bureau (University of Caen, France) for helpful discussions and Harald Lanig (University of Erlangen, Germany) for support with the simulations. Work in Erlangen was supported by the Deutsche Forschungsgemeinschaft as part of Graduiertenkolleg 1910 “Medicinal Chemistry of Selective GPCR Ligands”.

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Authors and Affiliations

  1. Centre for Molecular Design, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, PO1 2DT, UK

    Elke Haensele, Lee Banting, David C. Whitley & Timothy Clark

  2. Computer-Chemie-Centrum and Interdisciplinary Center for Molecular Materials, Friedrich-Alexander-Universität Erlangen-Nürnberg, Nägelsbachstraße 25, 91052, Erlangen, Germany

    Timothy Clark

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  1. Elke Haensele
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Correspondence to Timothy Clark.

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Glossary

Abs

Absolute

AMBER

Assisted Model Building with Energy Refinement

av

Average

AVP

8-Arginine-Vasopressin

cl.open

Clinched Open

DASH

Dynamics Analysis by Salt and Hudson

DMS

Dimethyl Sulfate

ff99sb

Force Field 1999 Stony Brooks

g/g′

gauche/gauche′

GPCR

G-Protein Coupled Receptor

Hbond

Hydrogen Bond

MD

Molecular Dynamics

NH

Amide Hydrogen

NP

Neurophysin

O

Carbonyl Oxygen

OT

Oxytocin

PC

Principle Component

PCA

Principle Component Analysis

PDB

Protein Data Bank

RadGyr

Radius of Gyration

Rel

Relative

RMSD

Root Mean Square Deviation

SDS

Sodium Dodecyl Sulfate

StdDev

Standard Deviation

T10

DASH analysis of torsions Φ/Ψ 2 to 6 (10 torsions)

T16

DASH analysis of torsions Φ/Ψ 2 to 9 (16 torsions)

TIP4P-Ew

Transferable Intermolecular Potential 4 Point - Ewald

TM

Trans Membrane

tw.saddle

Twisted Saddle

V2R

Vasopressin-2 receptor

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Haensele, E., Banting, L., Whitley, D.C. et al. Conformation and dynamics of 8-Arg-vasopressin in solution. J Mol Model 20, 2485 (2014). https://doi.org/10.1007/s00894-014-2485-0

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  • DOI: https://doi.org/10.1007/s00894-014-2485-0

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