Sampling the Folding Transition State Ensemble in a Tube-like Model of Protein

Nguyen Ba Hung, Trinh Xuan Hoang


We used the tube model with Go-like potential for native contacts to study the folding transition of a designed three-helix bundle and a designed protein G-like structure. It is shown that both proteins in this model are two-state folders with a cooperative folding transition coincided with the collapse transition. We defined the transition states as protein conformations in a small region around the saddle point on a free energy surface with the energy and the conformational
root mean square deviation (rmsd) from the native state as the coordinates. The transition state region on the free energy surface then was sampled by using umbrella sampling technique. We show that the transition state ensemble is broad consisting of different conformations that have different folded and unfolded elements.


free energy landscape, transition state, Monte Carlo simulation

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C. Levinthal, J. Chim. Phys. 65 (1968) 44–45.

P. E. Leopold, M. Montal and J. N. Onuchic, Proc. Natl. Acad. Sci. USA 89 (1992) 8721–8725.

P. G. Wolynes, J. N. Onuchic and D. Thirumalai, Science 267 (1995) 1619–1619.

A. Šali, E. Shakhnovich and M. Karplus, J. Mol. Biol. 235 (1994) 1614–1636.

J. N. Onuchic, N. D. Socci, Z. Luthey-Schulten and P. G. Wolynes, Fold. Des. 1 (1996) 441–450.

A. R. Fersht, A. Matouschek and L. Serrano, J. Mol. Biol. 224 (1992) 771–782.

D. E. Otzen, L. S. Itzhaki, S. Jackson and A. Fersht, Proc. Natl. Acad. Sci. USA 91 (1994) 10422–10425.

A. R. Fersht, L. S. Itzhaki, J. Matthews and D. Otzen, Proc. Natl. Acad. Sci. USA 91 (1994) 10426–10429.

H. M. Went and S. E. Jackson, Prot. Eng. Des. Sel. 18 (2005) 229–237.

J. C. Martinez, M. T. Pisabarro and L. Serrano, Nat. Struct. Mol. Biol. 5 (1998) 721.

T. X. Hoang and M. Cieplak, J. Chem. Phys. 112 (2000) 6851–6862.

T. X. Hoang and M. Cieplak, J. Chem. Phys. 113 (2000) 8319–8328.

C. Clementi, H. Nymeyer and J. N. Onuchic, J. Mol. Biol. 298 (2000) 937–953.

C. Clementi, A. E. Garcıa and J. N. Onuchic, J. Mol. Biol. 326 (2003) 933–954.

N. B. Hung and T. X. Hoang, Commun. Phys. 23 (2013) 313.

T. X. Hoang, A. Trovato, F. Seno, J. R. Banavar and A. Maritan, Proc. Natl. Acad. Sci. USA 101 (2004) 7960–7964.

N. Go, Ann. Rev. Biophys. Bioeng. 12 (1983) 183–210.

A. Maritan, C. Micheletti, A. Trovato and J. R. Banavar, Nature (London) 406 (2000) 287–290.

J. R. Banavar, T. X. Hoang, A. Maritan, F. Seno and A. Trovato, Phys. Rev. E 70 (2004) 041905.

T. X. Hoang, L. Marsella, A. Trovato, F. Seno, J. R. Banavar and A. Maritan, Proc. Natl. Acad. Sci. USA 103

(2006) 6883–6888.

R. H. Swendsen and J.-S. Wang, Phys. Rev. Lett. 57 (1986) 2607.

A. M. Ferrenberg and R. H. Swendsen, Phys. Rev. Lett. 63 (1989) 1195.

G. M. Torrie and J. P. Valleau, J. Comp. Phys. 23 (1977) 187–199.

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