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Misfolding of a polyalanine variant due to lack of electrostatic polarization effects

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Abstract

Folding of a polyalanine variant (A-AQ12 with the sequence Ac-[AAQAA]2-GY-NH2) in pure water is studied with molecular dynamics (MD) simulation using AMBER fixed charge model and AHBC charge variation model, respectively. The results show that AMBER ostensibly misfolds A-AQ12 into a well-defined α-helix, while A-AQ12 remains a random coil in AHBC agreeing better with the experimental predication of low fractional helical content. The difference is most likely due to the different backbone solvation with and without the incorporation of electrostatic polarization in the simulations, which highlights the importance of electrostatic polarization in H-bonds dynamics of α-helix in water.

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References

  1. Chou PY, Fasman GD (1974) Biochemistry 13:211

    Article  CAS  Google Scholar 

  2. Barlow DJ, Thornton JM (1988) J Mol Biol 201:601

    Article  CAS  Google Scholar 

  3. Baldwin RL, Rose GD (1999) TIBS. 24:22

    Google Scholar 

  4. Selkoe JD (2003) Nature 426:900–904

    Article  CAS  Google Scholar 

  5. Baldwin RL (1995) Biophys Chem 55:127

    Article  CAS  Google Scholar 

  6. Padmanabhan S, Baldwin RL (1994) Protein Sci 3:1992

    Article  CAS  Google Scholar 

  7. Chakrabartty A, Kortemme T, Baldwin RL (1994) Protein Sci 3:843

    Article  CAS  Google Scholar 

  8. Marqusee S, Robbins VH, Baldwin RL (1989) Proc Natl Acad Sci USA 86:5286

    Article  CAS  Google Scholar 

  9. Xu ZJ, Lazim R, Sun TD, Mei Y, Zhang DW (2012) J. Chem. Phys. 136:135102

    Article  Google Scholar 

  10. Kennedy RJ, Tsang KY, Kemp DS (2002) J Am Chem Soc 124:934

    Article  CAS  Google Scholar 

  11. Forood B, Feliciano EJ, Nambiar KP (1993) Proc Natl Acad Sci 90:838

    Article  CAS  Google Scholar 

  12. Huyghues-Despointes BM, Klingler TM, Baldwin RL (1995) Biochemistry 34:13267

    Article  CAS  Google Scholar 

  13. Stapley BJ, Doig AJ (1997) J Mol Biol 272:465

    Article  CAS  Google Scholar 

  14. Horovitz A, Serrano L, Avron B, Bycroft M, Fersht AR (1990) J Mol Biol 216:1031

    Article  CAS  Google Scholar 

  15. Padmanabhan S, Baldwin RL (1994) J Mol Biol 241:706

    Article  CAS  Google Scholar 

  16. Viguera AR, Serrano L (1995) Biochemistry 34:8771

    Article  CAS  Google Scholar 

  17. Taylor JW (2002) Biopolymers 66:49

    Article  CAS  Google Scholar 

  18. Pauling L, Corey RB, Branson HR (1951) Proc Natl Acad Sci USA 37:205

    Article  CAS  Google Scholar 

  19. Klotz IM, Farnham SB (1968) Biochemistry 7:3879

    Article  CAS  Google Scholar 

  20. Rohl CA, Baldwin RL (1998) Methods Enzymol 295:1

    Article  CAS  Google Scholar 

  21. Ma N, Chung Y-H, van der Vaart A (2013) J Comput Chem 34:640

    Google Scholar 

  22. McCammon JA, Gelin BR, Karplus M (1977) Nature 267:585

    Article  CAS  Google Scholar 

  23. Brooks BR, Karplus M (1983) Proc Natl Acad Sci USA 80:6571

    Article  CAS  Google Scholar 

  24. Shea JE, Brooks CL (2001) Annu Rev Phys Chem 52:499

    Article  CAS  Google Scholar 

  25. Case DA, Karplus M (1979) J Mol Biol 132:343

    Article  CAS  Google Scholar 

  26. Deng YQ, Roux B (2009) J. Phys. Chem. B. 113:2234

    Article  CAS  Google Scholar 

  27. Wei CY, Mei Y, Zhang DW (2010) Chem Phys Lett 495:121

    Article  CAS  Google Scholar 

  28. Lu YP, Mei Y, Zhang JZH, Zhang DW (2010) J. Chem. Phys 132:121101

    Article  Google Scholar 

  29. Scott WRP, Hünenberger PH, Tironi IG, Mark AE, Billeter SR, Fennen J, Torda AE, Huber T, Krüger P, van Gunsteren WF (1999) J Phys Chem A 103:3596

    Article  CAS  Google Scholar 

  30. Weiner PW, Kollman PA (1981) J Comput Chem 2:287

    Article  CAS  Google Scholar 

  31. Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M (1983) J Comput Chem 4:187

    Article  CAS  Google Scholar 

  32. Duan LL, Mei Y, Zhang QG, Zhang JZH (2009) J. Chem. Phys. 130:115102

    Article  Google Scholar 

  33. Ji CG, Mei Y, Zhang JZH (2008) Biophys J 95:1080

    Article  CAS  Google Scholar 

  34. Ji CG, Zhang JZH (2008) J Am Chem Soc 130:17129

    Article  CAS  Google Scholar 

  35. Hol WGJ (1985) Prog Biophys Mol Biol 45:149

    Article  CAS  Google Scholar 

  36. Kaminski GA, Stern HA, Berne BJ, Friesner RA, Cao YX, Murphy RB, Zhou RH, Halgren TA (2002) J Comput Chem 23:1515

    Article  CAS  Google Scholar 

  37. Chipot C, Angyan J, Maigret B (1993) J Phys Chem 97:9788

    Article  CAS  Google Scholar 

  38. Gao J, Truhlar DG (2002) Annu Rev Phys Chem 53:467

    Article  CAS  Google Scholar 

  39. Mei Y, Ji CG, Zhang JZH (2006) J. Chem. Phys. 125:94906

    Article  Google Scholar 

  40. Ji CG, Xiao XD, Zhang JZH (2012) J. Chem. Theor. Comput. 9:2157

    Article  Google Scholar 

  41. Duan LL, Gao Y, Mei Y, Zhang QG, Tang B, Zhang JZH (2012) J. Phys. Chem. B 116:3430

    Article  CAS  Google Scholar 

  42. Lin ZX, Schmid N, van Gunsteren WF (2011) Mol Phys 109:493

    Article  CAS  Google Scholar 

  43. Zhang DW, Zhang JZH (2003) J. Chem. Phys. 119:3599

    Article  CAS  Google Scholar 

  44. Gao AM, Zhang DW, Zhang JZH, Zhang YK (2004) Chem Phys Lett 394:293

    Article  CAS  Google Scholar 

  45. Tong Y, Ji CG, Mei Y, Zhang JZH (2009) J Am Chem Soc 131:8636

    Article  CAS  Google Scholar 

  46. Wei CY, Tung D, Mei Y, Zhang DW (2011) J. Chem. Phys. 134:171101

    Article  Google Scholar 

  47. Rohl CA, Chakrabartty A, Baldwin RL (1996) Protein Sci 5:2623

    Article  CAS  Google Scholar 

  48. Bayly CI, Cieplak P, Cornell WD, Kollman PA (1993) J Phys Chem 97:10269

    Article  CAS  Google Scholar 

  49. Bayly CI, Cieplak P, Cornell WD, Kollman PA (1993) J Phys Chem 115:9620

    Google Scholar 

  50. Rocchia W, Sridharan S, Nicholls A, Alexov E, Chiabrera A, Honig B (2002) J. Comp. Chem. 23:128

    Article  CAS  Google Scholar 

  51. McDonald IK, Thornton JM (1994) J Mol Biol 238:777

    Article  CAS  Google Scholar 

  52. Case DA, Darden TA, Cheatham TE III, Simmerling CL, Wang J, Duke RE, Luo R, Crowley M, Walker RC, Zhang W, Merz KM, Wang B, Hayik S, Roitberg A, Seabra G, Kolossváry I, Wong KF, Paesani F, Vanicek J, Wu X, Brozell SR, Steinbrecher T, Gohlke H, Yang L, Tan C, Mongan J, Hornak V, Cui G, Mathews DH, Seetin MG, Sagui C, Babin V, Kollman PA (2008) AMBER 10. University of California, San Francisco

    Google Scholar 

  53. Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML (1983) J. Chem. Phys. 79:926

    Article  CAS  Google Scholar 

  54. Pastor RW, Brooks BR, Szabo A (1988) Mol Phys 65:1409

    Article  Google Scholar 

  55. Rychaert J, Ciccotti G, Berendsen HJC (1977) J Comput Phys 23:327

    Article  Google Scholar 

  56. Vila J, Williams RL, Grants JA, Wojcik J, Scheraga HA (1992) Proc Natl Acad Sci 89:7821

    Article  CAS  Google Scholar 

  57. Kabsch W, Sander C (1983) Biopolymers 22:2577

    Article  CAS  Google Scholar 

  58. Humphrey W, Alke A, Schulten K (1996) J Mol Graph 14:33

    Article  CAS  Google Scholar 

  59. Millhauser GL (1995) Biochemistry 34:3873

    Article  CAS  Google Scholar 

  60. Bolin KA, Millhauser GL (1999) Acc Chem Res 32:1027

    Article  CAS  Google Scholar 

  61. Shao J, Tanner SW, Thompson N, Cheatham TE (2007) J Chem Theory Comput 3:2312

    Article  CAS  Google Scholar 

  62. Lacroix E, Viguera AR, Serrano L (1998) J Mol Biol 284:173

    Article  CAS  Google Scholar 

Download references

Acknowledgments

D.W.Z. is supported in part by Nanyang Technological University start-up grant, and in part by Singapore AcRF Tier 1 Grant RG58/11 and COS collaborative research. D.W.Z. thanks NTU HPC support and resources.

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Authors and Affiliations

  1. Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, 637371, Singapore

    Tiedong Sun, Caiyi Wei, Ni Wei Charlie Neo & Dawei Zhang

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  1. Tiedong Sun
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  2. Caiyi Wei
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  3. Ni Wei Charlie Neo
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  4. Dawei Zhang
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Corresponding author

Correspondence to Dawei Zhang.

Additional information

Tiedong Sun and Caiyi Wei contributed equally to this work.

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Sun, T., Wei, C., Neo, N.W.C. et al. Misfolding of a polyalanine variant due to lack of electrostatic polarization effects. Theor Chem Acc 132, 1354 (2013). https://doi.org/10.1007/s00214-013-1354-8

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