Skip to main content
NCBI home page
Journal of Biological Physics logoLink to Journal of Biological Physics
. 2001 Jun;27(2-3):169–179. doi: 10.1023/A:1013155018382

Hydrogen Bonds, Hydrophobicity Forces and the Character of the Collapse Transition

A Irbäck 1, F Sjunnesson 1, S Wallin 1
PMCID: PMC3456579  PMID: 23345742

Abstract

We study the thermodynamic behavior of a model protein with 54 amino acidsthat is designed to form a three-helix bundle in its native state. The model contains three types of amino acids and five to six atoms per amino acid, and has the Ramachandran torsion angles as its only degrees of freedom.The force field is based on hydrogen bonds and effective hydrophobicity forces. We study how the character of the collapse transition depends on the strengths of these forces. For a suitable choice of these two parameters, it is found that the collapse transition is first-order-like and coincides with the folding transition. Also shown is that the corresponding one- and two-helix segments make less stable secondary structure than the three-helix sequence.

Keywords: Folding thermodynamics, hydrogen bonds, hydrophobicity, protein folding

Full Text

The Full Text of this article is available as a PDF (213.0 KB).

References

  • 1.Gō N., Taketomi H. Respective Roles of Short-and Long-Range Interactions in Protein Folding. Proc. Natl. Acad. Sci. USA. 1978;75:559–563. doi: 10.1073/pnas.75.2.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Săli A., Shakhnovich E., Karplus M. Kinetics of Protein Folding: A Lattice Model Study of the Requirements for Folding to the Native State. J. Mol. Biol. 1994;235:1614–1636. doi: 10.1006/jmbi.1994.1110. [DOI] [PubMed] [Google Scholar]
  • 3.Bryngelson J.D., Onuchic J.N., Socci N.D., Wolynes P.G. Funnels, Pathways, and the Energy Landscape of Protein Folding: A Synthesis. Proteins: Struct. Funct. Genet. 1995;21:167–195. doi: 10.1002/prot.340210302. [DOI] [PubMed] [Google Scholar]
  • 4.Dill K.A., Chan H.S. From Levinthal to Pathways to Funnels. Nature Struct. Biol. 1997;4:10–19. doi: 10.1038/nsb0197-10. [DOI] [PubMed] [Google Scholar]
  • 5.Klimov D.K., Thirumalai D. Linking Rates of Folding in Lattice Models of Proteins with Underlying Thermodynamic Characteristics. J. Chem. Phys. 1998;109:4119–4125. [Google Scholar]
  • 6.Nymeyer H., García A.E., Onuchic J.N. Folding Funnels and Frustration in Off-Lattice Minimalist Protein Landscapes. Proc. Natl. Acad. Sci. USA. 1998;95:5921–5928. doi: 10.1073/pnas.95.11.5921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Socci N.D., Bialek W.S., Onuchic J.N. Properties and Origins of Protein Secondary Structure. Phys. Rev. E. 1994;49:3440–3443. doi: 10.1103/physreve.49.3440. [DOI] [PubMed] [Google Scholar]
  • 8.Irbäck A., Peterson C., Potthast F., Sommelius O. Local Interactions and Protein Folding: A Three-Dimensional Off-Lattice Approach. J. Chem. Phys. 1997;107:273–282. [Google Scholar]
  • 9.Vendruscolo M., Najmanovich R., Domany E. Protein Folding in Contact Map Space. Phys. Rev. Lett. 1999;82:656–659. [Google Scholar]
  • 10.Alm E., Baker D. Matching Theory and Experiment in Protein Folding. Curr. Opin. Struct. Biol. 1999;9:189–196. doi: 10.1016/S0959-440X(99)80027-X. [DOI] [PubMed] [Google Scholar]
  • 11.Irbäck A., Sjunnesson F., Wallin S. Three-Helix-Bundle Protein in a Ramachandran Model. Proc. Natl. Acad. Sci. USA. 2000;97:13614–13618. doi: 10.1073/pnas.240245297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Ramachandran G.N., Sasisekharan V. Conformation of Polypeptides and Proteins. Adv. Protein Chem. 1968;23:283–437. doi: 10.1016/s0065-3233(08)60402-7. [DOI] [PubMed] [Google Scholar]
  • 13.Regan L., DeGrado W.F. Characterization of a Helical Protein Designed from First Principles. Science. 1988;241:976–978. doi: 10.1126/science.3043666. [DOI] [PubMed] [Google Scholar]
  • 14.Lyubartsev A.P., Martsinovski A.A., Shevkunov S.V., Vorontsov-Velyaminov P.V. New Approach to Monte Carlo Calculation of the Free Energy: Method of Expanded Ensembles. J. Chem. Phys. 1992;96:1776–1783. [Google Scholar]
  • 15.Marinari E., Parisi G. Simulated Tempering: A New Monte Carlo Scheme. Europhys. Lett. 1992;19:451–458. [Google Scholar]
  • 16.Irbäck A., Potthast F. Studies of an Off-Lattice Model for Protein Folding: Sequence Dependence and Improved Sampling at Finite Temperature. J. Chem. Phys. 1995;103:10298–10305. [Google Scholar]
  • 17.Shea J.-E., Nochomovitz Y.D., Guo Z., Brooks C.L., III Exploring the Space of Protein Folding Hamiltonians: The Balance of Forces in a Minimalist β-Barrel Model. J. Chem. Phys. 1998;109:2895–2903. [Google Scholar]
  • 18.Shea J.-E., Onuchic J.N., Brooks C.L., III Exploring the Origins of Topological Frustration: Design of a Minimally Frustrated Model of Fragment B of Protein A. Proc. Natl. Acad. Sci. USA. 1999;96:12512–12517. doi: 10.1073/pnas.96.22.12512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Clementi C., Jennings P.A., Onuchic J.N. How Native-State Topology Affects the Folding of Dihydrofolate Reductase and Interleukin-1/α. Proc. Natl. Acad. Sci. USA. 2000;97:5871–5876. doi: 10.1073/pnas.100547897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Clementi C., Nymeyer H., Onuchic J.N. Topological and Energetic Factors: What Determines the Structural Details of the Transition State Ensemble and “En-Route” Intermediates for Protein Folding? An Investigation for Small Globular Proteins. J. Mol. Biol. 2000;298:937–953. doi: 10.1006/jmbi.2000.3693. [DOI] [PubMed] [Google Scholar]
  • 21.Shimada J., Kussell E.L., Shakhnovich E.I. The Folding Thermodynamics and Kinetics of Crambin Using an All-Atom Monte Carlo Simulation. J. Mol. Biol. 2001;308:79–95. doi: 10.1006/jmbi.2001.4586. [DOI] [PubMed] [Google Scholar]
  • 22.Rey A., Skolnick J. Computer Modeling and Folding of Four-Helix Bundles. Proteins: Struct. Funct. Genet. 1993;16:8–28. doi: 10.1002/prot.340160103. [DOI] [PubMed] [Google Scholar]
  • 23.Guo Z., Thirumalai D. Kinetics and Thermodynamics of Folding of a de novo Designed Four-Helix Bundle Protein. J. Mol. Biol. 1996;263:323–343. doi: 10.1006/jmbi.1996.0578. [DOI] [PubMed] [Google Scholar]
  • 24.Zhou Z., Karplus M. Folding Thermodynamics of a Model Three-Helix-Bundle Protein. Proc. Natl. Acad. Sci. USA. 1997;94:14429–14432. doi: 10.1073/pnas.94.26.14429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Koretke K.K., Luthey-Schulten Z., Wolynes P.G. Self-Consistently Optimized Energy Functions for Protein Structure Prediction by Molecular Dynamics. Proc. Natl. Acad. Sci. USA. 1998;95:2932–2937. doi: 10.1073/pnas.95.6.2932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Hardin C., Luthey-Schulten Z., Wolynes P.G. Backbone Dynamics, Fast Folding, and Secondary Structure Formation in Helical Proteins and Peptides. Proteins: Struct. Funct. Genet. 1999;34:281–294. [PubMed] [Google Scholar]
  • 27.Takada S., Luthey-Schulten Z., Wolynes P.G. Folding Dynamics With Nonadditive Forces: A Simulation Study of a Designed Helical Protein and a Random Heteropolymer. J. Chem. Phys. 1999;110:11616–11629. [Google Scholar]
  • 28.Ferrenberg A.M., Swendsen R.H. NewMonte Carlo for Studying Phase Transitions. Phys. Rev. Lett. 1988;61:2635–2638. doi: 10.1103/PhysRevLett.61.2635. [DOI] [PubMed] [Google Scholar]
  • 29.Sayle R., Milner-White E.J. RasMol: Biomolecular Graphics for All. Trends Biochem. Sci. 1995;20:374–376. doi: 10.1016/s0968-0004(00)89080-5. [DOI] [PubMed] [Google Scholar]
  • 30.Kolinski A., Skolnick J., Yaris R. Monte Carlo Simulations on an Equilibrium Globular Protein Folding Model. Proc. Natl. Acad. Sci. USA. 1986;83:7267–7271. doi: 10.1073/pnas.83.19.7267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Doniach S., Garel T., Orland H. Phase Diagram of a Semiflexible Polymer Chain in a α Solvent: Application to Protein Folding. J. Chem. Phys. 1996;105:1601–1608. [Google Scholar]
  • 32.Bastolla U., Grassberger P. Phase Transitions of Single Semi-Stiff Polymer Chains. J. Stat. Phys. 1997;89:1061–1078. [Google Scholar]
  • 33.Doye J.P.K., Sear R.P., Frenkel D. The Effect of Chain Stiffness on the Phase Behaviour of Isolated Homopolymers. J. Chem. Phys. 1998;108:2134–2142. [Google Scholar]

Articles from Journal of Biological Physics are provided here courtesy of Springer Science+Business Media B.V.

RESOURCES