Sequence of Events in Folding Mechanism: Beyond the Gō Model

Overview

Journal Protein Sci

Specialty Biochemistry

Date 2006 Jul 4

PMID 16815916

Citations 11

Authors

Ludovico Sutto

Guido Tiana

Ricardo A Broglia

Affiliations

Soon will be listed here.

Abstract

Simplified Gō models, where only native contacts interact favorably, have proven useful to characterize some aspects of the folding of small proteins. The success of these models is limited by the fact that all residues interact in the same way so that the folding features of a protein are determined only by the geometry of its native conformation. We present an extended version of a Calpha-based Gō model where different residues interact with different energies. The model is used to calculate the thermodynamics of three small proteins (Protein G, Src-SH3, and CI2) and the effect of mutations (DeltaDeltaGU-N, DeltaDeltaGdouble dagger-N, DeltaDeltaGdouble dagger-U, and phi-values) on the wild-type sequence. The model allows us to investigate some of the most controversial areas in protein folding, such as its earliest stages and the nature of the unfolded state, subjects that have lately received particular attention.

Citing Articles

Multi-GO: Model Improvements toward the Study of Complex Self-Assembly Processes.

Toplek F, Scalone E, Stegani B, Paissoni C, Capelli R, Camilloni C J Chem Theory Comput. 2023; 20(1):459-468.

PMID: 38153340 PMC: 10782439. DOI: 10.1021/acs.jctc.3c01182.

Thermodynamics of strongly allosteric inhibition: a model study of HIV-1 protease.

Kimura S, Broglia R, Tiana G Eur Biophys J. 2012; 41(11):991-1001.

PMID: 23052976 DOI: 10.1007/s00249-012-0862-0.

Non-native interactions play an effective role in protein folding dynamics.

Faisca P, Nunes A, Travasso R, Shakhnovich E Protein Sci. 2010; 19(11):2196-209.

PMID: 20836137 PMC: 3005790. DOI: 10.1002/pro.498.

Analysis of the free-energy surface of proteins from reversible folding simulations.

Allen L, Krivov S, Paci E PLoS Comput Biol. 2009; 5(7):e1000428.

PMID: 19593364 PMC: 2700257. DOI: 10.1371/journal.pcbi.1000428.

Insights from coarse-grained Gō models for protein folding and dynamics.

Hills Jr R, Brooks 3rd C Int J Mol Sci. 2009; 10(3):889-905.

PMID: 19399227 PMC: 2672008. DOI: 10.3390/ijms10030889.

References

Clementi C, Nymeyer H, Onuchic J . 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(5):937-53. DOI: 10.1006/jmbi.2000.3693. View

Religa T, Markson J, Mayor U, Freund S, Fersht A . Solution structure of a protein denatured state and folding intermediate. Nature. 2005; 437(7061):1053-6. DOI: 10.1038/nature04054. View

McCallister E, Alm E, Baker D . Critical role of beta-hairpin formation in protein G folding. Nat Struct Biol. 2000; 7(8):669-73. DOI: 10.1038/77971. View

Riddle D, Grantcharova V, Santiago J, Alm E, Ruczinski I, Baker D . Experiment and theory highlight role of native state topology in SH3 folding. Nat Struct Biol. 1999; 6(11):1016-24. DOI: 10.1038/14901. View

Kazmirski S, Wong K, Freund S, Tan Y, Fersht A, Daggett V . Protein folding from a highly disordered denatured state: the folding pathway of chymotrypsin inhibitor 2 at atomic resolution. Proc Natl Acad Sci U S A. 2001; 98(8):4349-54. PMC: 31838. DOI: 10.1073/pnas.071054398. View

Li L, Shakhnovich E . Constructing, verifying, and dissecting the folding transition state of chymotrypsin inhibitor 2 with all-atom simulations. Proc Natl Acad Sci U S A. 2001; 98(23):13014-8. PMC: 60816. DOI: 10.1073/pnas.241378398. View

Broglia R, Tiana G . Reading the three-dimensional structure of lattice model-designed proteins from their amino acid sequence. Proteins. 2001; 45(4):421-7. DOI: 10.1002/prot.1158. View

Borreguero J, Dokholyan N, Buldyrev S, Shakhnovich E, Stanley H . Thermodynamics and folding kinetics analysis of the SH3 domain form discrete molecular dynamics. J Mol Biol. 2002; 318(3):863-76. DOI: 10.1016/S0022-2836(02)00136-5. View

Guerois R, Nielsen J, Serrano L . Predicting changes in the stability of proteins and protein complexes: a study of more than 1000 mutations. J Mol Biol. 2002; 320(2):369-87. DOI: 10.1016/S0022-2836(02)00442-4. View

10.

Shimada J, Shakhnovich E . The ensemble folding kinetics of protein G from an all-atom Monte Carlo simulation. Proc Natl Acad Sci U S A. 2002; 99(17):11175-80. PMC: 123229. DOI: 10.1073/pnas.162268099. View

11.

Karanicolas J, Brooks 3rd C . The origins of asymmetry in the folding transition states of protein L and protein G. Protein Sci. 2002; 11(10):2351-61. PMC: 2373711. DOI: 10.1110/ps.0205402. View

12.

Khan F, Chuang J, Gianni S, Fersht A . The kinetic pathway of folding of barnase. J Mol Biol. 2003; 333(1):169-86. DOI: 10.1016/j.jmb.2003.08.024. View

13.

Onuchic J, Wolynes P . Theory of protein folding. Curr Opin Struct Biol. 2004; 14(1):70-5. DOI: 10.1016/j.sbi.2004.01.009. View

14.

Lindorff-Larsen K, Vendruscolo M, Paci E, Dobson C . Transition states for protein folding have native topologies despite high structural variability. Nat Struct Mol Biol. 2004; 11(5):443-9. DOI: 10.1038/nsmb765. View

15.

Levy Y, Caflisch A, Onuchic J, Wolynes P . The folding and dimerization of HIV-1 protease: evidence for a stable monomer from simulations. J Mol Biol. 2004; 340(1):67-79. DOI: 10.1016/j.jmb.2004.04.028. View

16.

Matysiak S, Clementi C . Optimal combination of theory and experiment for the characterization of the protein folding landscape of S6: how far can a minimalist model go?. J Mol Biol. 2004; 343(1):235-48. DOI: 10.1016/j.jmb.2004.08.006. View

17.

PTITSYN O, Rashin A . A model of myoglobin self-organization. Biophys Chem. 1975; 3(1):1-20. DOI: 10.1016/0301-4622(75)80033-0. View

18.

Karplus M, Weaver D . Protein-folding dynamics. Nature. 1976; 260(5550):404-6. DOI: 10.1038/260404a0. View

19.

Lesk A, Rose G . Folding units in globular proteins. Proc Natl Acad Sci U S A. 1981; 78(7):4304-8. PMC: 319778. DOI: 10.1073/pnas.78.7.4304. View

20.

Go N . Theoretical studies of protein folding. Annu Rev Biophys Bioeng. 1983; 12:183-210. DOI: 10.1146/annurev.bb.12.060183.001151. View