Skip to main content
SpringerLink
Log in

Combined effect of confinement and affinity of crowded environment on conformation switching of adenylate kinase

  • Original Paper
  • Published:
Journal of Molecular Modeling Aims and scope Submit manuscript

Abstract

The actual conformation switching of proteins in the crowded cellular environment is completely different from that in vitro. Proteins in cytoplasm are continually subject to confinement and/or attraction to other molecules in their surroundings due to the existence of various biological species. To gain insight into the nature of crowded environments, we investigated the effects of confinement and affinity on the conformation switching of adenylate kinase (ADK) in a spherical cavity. It was found that even a small degree of confinement reduces the entropy of the open state and stabilizes the closed state, which leads to increased energy barriers for transition. Furthermore, the analysis of transition temperatures and mean first passage times indicates that the proper affinity can promote the transition of ADK from closed state to open state. This study reveals that the crowded cellular environment plays an important role in the thermodynamics and kinetics of proteins in vivo.

Cartoon representation of adenylate kinase in a spherical cavity. The LID, NMPand Core domains are highlighted in yellow, blue and magenta, respectively

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Ellis R (2001) J Curr Opin Struct Biol 11:500

    Article  CAS  Google Scholar 

  2. Minton AP (2005) J Pharm Sci 94:1668

    Article  CAS  Google Scholar 

  3. Ellis RJ, Minton AP (2003) Nature 425:27

    Article  CAS  Google Scholar 

  4. Minton AP (2001) J Biol Chem 276:10577

    Article  CAS  Google Scholar 

  5. Minton AP (1983) Mol Cell Biochem 55:119

    Article  CAS  Google Scholar 

  6. Minton AP (1998) Methods Enzymol 295:127

    Article  CAS  Google Scholar 

  7. Zimmerman SB, Minton AP (1993) Annu Rev Biophys Biomol Struct 22:27

    Article  CAS  Google Scholar 

  8. Zimmerman SB, Trach SO (1991) J Mol Biol 222:599

    Article  CAS  Google Scholar 

  9. Friedel M, Sheeler DJ, Shea JE (2003) J Chem Phys 118:8106

    Article  CAS  Google Scholar 

  10. Eggers DK, Valentine JS (2001) Protein Sci 10:250

    Article  CAS  Google Scholar 

  11. Eggers DK, Valentine JS (2001) J Mol Biol 314:911

    Article  CAS  Google Scholar 

  12. Lei C, Shin Y, Liu J, Ackerman EJ (2002) J Am Chem Soc 124:11242

    Article  CAS  Google Scholar 

  13. Wang YQ, Sarkar M, Smith AE, Krois AS, Pielak GJ (2012) J Am Chem Soc 134:16614

    Article  CAS  Google Scholar 

  14. Arkin H, Janke W (2012) J Phys Chem B 116:10379

    Article  CAS  Google Scholar 

  15. Chen E, Christiansen A, Wang Q, Cheung MS, Kliger DS, Wittung-Stafshede P (2012) Biochemistry 51:9836

    Article  CAS  Google Scholar 

  16. Klimov DK, Newfield D, Thirumalai D (2002) Proc Natl Acad Sci USA 99:8019

    Article  CAS  Google Scholar 

  17. Kurniawan NA, Enemark S, Rajagopalan R (2012) J Am Chem Soc 134:10200

    Article  CAS  Google Scholar 

  18. Lucent D, Vishal V, Pande VS (2007) Proc Natl Acad Sci USA 104:10430

    Article  CAS  Google Scholar 

  19. Malik A, Kundu J, Mukherjee SK, Chowdhury PK (2012) J Phys Chem B 116:12895

    Article  CAS  Google Scholar 

  20. Marino KA, Bolhuis PG (2012) J Phys Chem B 116:11872

    Article  CAS  Google Scholar 

  21. Martin J (2004) J Mol Recognit 17:465

    Article  CAS  Google Scholar 

  22. Mittal J, Best RB (2008) Proc Natl Acad Sci USA 105:20233

    Article  CAS  Google Scholar 

  23. Predeus AV, Gul S, Gopal SM, Feig M (2012) J Phys Chem B 116:8610

    Article  CAS  Google Scholar 

  24. Rao JS, Cruz L (2013) J Phys Chem B 117:3707

    Article  CAS  Google Scholar 

  25. Rathore N, Knotts TA, de Pablo J (2006) J Biophys J 90:1767

    Article  CAS  Google Scholar 

  26. Wojciehowski M, Cieplak M (2008) Biosystems 94:248

    Article  Google Scholar 

  27. Xu WX, Wang J, Wang W (2005) Proteins 61:777

    Article  CAS  Google Scholar 

  28. Wang W, Xu WX, Levy Y, Trizac E, Wolynes PG (2009) Proc Natl Acad Sci USA 106:5517

    Article  CAS  Google Scholar 

  29. Benton LA, Smith AE, Young GB, Pielak G (2012) J Biochem 51:9773

    Article  CAS  Google Scholar 

  30. Zhou HX (2004) J Mol Recognit 17:368

    Article  CAS  Google Scholar 

  31. Zhou HX, Dill KA (2001) Biochemistry 40:11289

    Article  CAS  Google Scholar 

  32. Nakamura HK, Sasai M, Takano M (2004) Chem Phys 307:259

    Article  CAS  Google Scholar 

  33. Cieplak M, Hoang TX, Robbins MO (2002) Proteins 49:114

    Article  CAS  Google Scholar 

  34. Hayward S, Go N (1995) Annu Rev Phys Chem 46:223

    Article  CAS  Google Scholar 

  35. Kim J, Keyes T (2008) J Phys Chem B 112:954

    Article  CAS  Google Scholar 

  36. Ueeda Y, Taketomi H, Go N (1978) Bioplymers 17:1531

    Article  Google Scholar 

  37. Hills RD, Brooks CL (2009) Int J Mol Sci 10:889

    Article  CAS  Google Scholar 

  38. Lu Q, Wang J (2008) J Am Chem Soc 130:4772

    Article  CAS  Google Scholar 

  39. Whitford PC, Miyashita O, Levy Y, Onuchic JN (2007) J Mol Biol 366:1661

    Article  CAS  Google Scholar 

  40. Daily MD, Phillips GN, Cui QA (2010) J Mol Biol 400:618

    Article  CAS  Google Scholar 

  41. Beckstein O, Denning EJ, Perilla JR, Woolf TB (2009) J Mol Biol 394:160

    Article  CAS  Google Scholar 

  42. Lai ZZ, Lu Q, Wang J (2011) J Phys Chem B 115:4147

    Article  CAS  Google Scholar 

  43. Chu JW, Voth GA (2007) Biophys J 93:3860

    Article  CAS  Google Scholar 

  44. Levy Y, Wolynes PG, Onuchic JN (2004) Proc Natl Acad Sci USA 101:511

    Article  CAS  Google Scholar 

  45. Lu Q, Wang J (2009) J Phys Chem B 113:1517

    Article  CAS  Google Scholar 

  46. Cellmer T, Bratko D, Blanch H (2003) Biophys J 84:41a

    Google Scholar 

  47. Dukovski I, Muthukumar M (2003) J Chem Phys 118:6648

  48. Liu C, Muthukumar M (1998) J Chem Phys 109:2536

    Article  CAS  Google Scholar 

  49. Clementi C, Nymeyer H, Onuchic JN (2000) J Mol Biol 298:937

    Article  CAS  Google Scholar 

  50. Bryngelson JD, Onuchic JN, Socci ND, Wolynes PG (1995) Proteins 21:167

    Article  CAS  Google Scholar 

  51. Dill KA, Chan HS (1997) Nat Struct Biol 4:10

    Article  CAS  Google Scholar 

  52. Onuchic JN, LutheySchulten Z, Wolynes PG (1997) Annu Rev Phys Chem 48:545

    Article  CAS  Google Scholar 

  53. Wolynes PG (2005) Philos T R Soc A 363:453

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grants No. 21433004 and 21473056), Shanghai Pu Jiang Program (12PJ1403000), Shanghai Natural Science Foundation (14ZR1411800) and a start-up grant of ECNU (41500-515430-14100/001/136). We also thank the supercomputer center of ECNU for computer time.

Author information

Authors and Affiliations

  1. State Key Laboratory of Precision Spectroscopy, Institute of Theoretical and Computational Science, East China Normal University, Shanghai, 200062, China

    Min Li & John Z. H. Zhang

  2. Institute for Advanced Interdisciplinary Research, East China Normal University, Shanghai, 200062, China

    Weixin Xu

  3. Department of Chemistry, East China Normal University, Shanghai, 200062, China

    Fei Xia

  4. NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai, 200062, China

    John Z. H. Zhang & Fei Xia

Authors
  1. Min Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weixin Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John Z. H. Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fei Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to John Z. H. Zhang or Fei Xia.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Fig. S1

Sampled trajectories obtained at temperatures T = 0.5 (a), 0.65 (b), 0.75 (c) and 0.95 (d). The black and red curves denote the calculated RMSD of closed and open states with respect to the number of steps N, respectively. (GIF 80 kb)

High Resolution (TIFF 98 kb)

Fig. S2

The 2D free energy profiles in bulk at temperatures T =  0.5 (a), 0.65 (b), 0.75 (c) and 0.95 (d) as a function of rmsd_close and rmsd_open in Ångstroms. The values of free energies range from 0.0 to 6.0 in units of K BTf 0. (GIF 136 kb)

High Resolution (TIFF 159 kb)

Fig. S3

The 2D free-energy profiles are obtained at the radii R =  5.0,(a), 9.5 (b) and 12 Å (c), where the different temperatures T = 0.50, 0.65 and 0.95 correspond to the plots from left to right, respectively, as functions of rmsd_close and rmsd_open in Ångstroms. The values of free energies range from 0.0 to 6.0 in units of KBTf 0. (GIF 148 kb)

High Resolution (TIFF 191 kb)

Fig. S4

The values of (Tf−Tf 0)/Tf 0 denoted by blue squares are approximately proportional to the function of R-3.75, which is indicated by the fitted red curve. (GIF 7 kb)

High Resolution (TIFF 13 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, M., Xu, W., Zhang, J.Z.H. et al. Combined effect of confinement and affinity of crowded environment on conformation switching of adenylate kinase. J Mol Model 20, 2530 (2014). https://doi.org/10.1007/s00894-014-2530-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00894-014-2530-z

Keywords

Search

Navigation