References
1. Dill KA, Shortle D. Denatured states of proteins. Annu. Rev. Biochem. 1991;60:795–825.
2. Morrone A, McCully ME, Bryan PN, Brunori M, Daggett V, Gianni S, Travaglini-Allocatelli C. The denatured state dictates the topology of two proteins with almost identical sequence but different native structure and function. J. Biol. Chem. 2011;286:3863–3872.
3. Shortle D. The denatured state (the other half of the folding equation) and its role in protein stability. FASEB J. 1996;10:27–34.
4. Fawzi NL, Chubukov V, Clark LA, Brown S, Head-Gordon T. Influence of denatured and intermediate states of folding on protein aggregation. Protein Sci. 2005;14:993–1003.
5. Hetz C, Chevet E, Harding HP. Targeting the unfolded protein response in disease. Nat. Rev. Drug Discov. 2013;12:703–719.
6. Alexandrescu AT, Abeygunawardana C, Shortle D. Structure and Dynamics of a Denatured 131-Residue Fragment of Staphylococcal Nuclease: A Heteronuclear NMR Study. Biochemistry. 1994;33:1063–1072.
7. Reed MAC, Jelinska C, Syson K, Cliff MJ, Splevins A, Alizadeh T, Hounslow AM, Staniforth RA, Clarke AR, Craven CJ, et al. The denatured state under native conditions: a non-native-like collapsed state of N-PGK. J. Mol. Biol. 2006;357:365–372.
8. Mok YK, Kay CM, Kay LE, Forman-Kay J. NOE data demonstrating a compact unfolded state for an SH3 domain under non-denaturing conditions. J. Mol. Biol. 1999;289:619–638.
9. Pfeil W, Privalov PL. Thermodynamic investigations of proteins. Biophys. Chem. 1976;4:23–32.
10. Tanford C, Kawahara K, Lapanje S. Proteins in 6 m Guanidine Hydrochloride: demonstration of random coil behavior. J. Biol. Chem. 1966;241:1921–1923.
11. Shortle D, Ackerman MS. Persistence of native-like topology in a denatured protein in 8 M urea. Science. 2001;293:487–489.
12. Rösner HI, Poulsen FM. Residue-specific description of non-native transient structures in the ensemble of acid-denatured structures of the all-beta protein c-src SH3. Biochemistry. 2010;49:3246–3253.
13. Sari N, Alexander P, Bryan PN, Orban J. Structure and Dynamics of an Acid-Denatured Protein G Mutant †. Biochemistry. 2000;39:965–977.
14. Teilum K, Thormann T, Caterer NR, Poulsen HI, Jensen PH, Knudsen J, Kragelund BB, Poulsen FM. Different secondary structure elements as scaffolds for protein folding transition states of two homologous four-helix bundles. Proteins Struct. Funct. Genet. 2005;59:80–90.
15. Wang Y, Shortle D. Residual helical and turn structure in the denatured state of staphylococcal nuclease: analysis of peptide fragments. Fold. Des. 1997;2:93–100.
16. Ackerman MS, Shortle D. Robustness of the long-range structure in denatured staphylococcal nuclease to changes in amino acid sequence. Biochemistry. 2002;41:13791–13797.
17. Bruun SW, Iesmantavicius V, Danielsson J, Poulsen FM. Cooperative formation of native-like tertiary contacts in the ensemble of unfolded states of a four-helix protein. Proc. Natl. Acad. Sci. U. S. A. 2010;107:13306–13311.
18. Ishima R, Torchia DA, Lynch SM, Gronenborn AM, Louis JM. Solution structure of the mature HIV-1 protease monomer: insight into the tertiary fold and stability of a precursor. J. Biol. Chem. 2003;278:43311–43319.
19. Broglia RA, Provasi D, Vasile F, Ottolina G, Longhi R, Tiana G. A folding inhibitor of the HIV-1 protease. Proteins Struct. Funct. Genet. 2005;62:928–933.
20. Broglia RA, Levy Y, Tiana G. HIV-1 protease folding and the design of drugs which do not create resistance. 2008;18:60–66.
21. Kimura S, Broglia RA, Tiana G. Thermodynamics of strongly allosteric inhibition: a model study of HIV-1 protease. Eur. Biophys. J. 2012 Oct 8:1–13.
22. Plaxco KW, Simons KT, Baker D. Contact order, transition state placement and the refolding rates of single domain proteins. J. Mol. Biol. 1998;277:985–994.
23. Kuzmic P. Kinetic assay for HIV proteinase subunit dissociation. Biochem. Biophys. Res. Commun. 1993;191:998–1003.
24. Noel AF, Bilsel O, Kundu A, Wu Y, Zitzewitz JA, Matthews CR. The folding free-energy surface of HIV-1 protease: insights into the thermodynamic basis for resistance to inhibitors. J. Mol. Biol. 2009;387:1002–1016.
25. Ishima R, Ghirlando R, Tözsér J, Gronenborn AM, Torchia DA, Louis JM. Folded monomer of HIV-1 protease. J. Biol. Chem. 2001;276:49110–49116.
26. Caldarini M, Sonar P, Valpapuram I, Tavella D, Volonté C, Pandini V, Vanoni MA, Aliverti A, Broglia RA, Tiana G, et al. The complex folding behavior of HIV-1-protease monomer revealed by optical-tweezer single-molecule experiments and molecular dynamics simulations. Biophys. Chem. 2014;195C:32–42.
27. Rösner HI, Caldarini M, Prestel A, Vanoni MA, Broglia RA, Aliverti A, Tiana G, Kragelund BB. Cold Denaturation of the HIV-1 Protease Monomer. Biochemistry. 2017;56:1029–1032.
28. Tomasselli AG, Heinrikson RL. Targeting the HIV-protease in AIDS therapy: a current clinical perspective. Biochim. Biophys. Acta. 2000;1477:189–214.
29. Cecconi F, Micheletti C, Carloni P, Maritan A. Molecular dynamics studies on HIV-1 protease drug resistance and folding pathways. Proteins Struct. Funct. Genet. 2001;43:365–372.
30. Kimura S, Caldarini M, Broglia RA, Dokholyan N V, Tiana G. The maturation of HIV-1 protease precursor studied by discrete molecular dynamics. Proteins Struct. Funct. Genet. 2014;82:633–639.
31. Bhavesh NS, Panchal SC, Mittal R, Hosur R V. NMR identification of local structural preferences in HIV-1 protease tethered heterodimer in 6 M guanidine hydrochloride. FEBS Lett. 2001;509:218–224.
32. Bhavesh NS, Sinha R, Mohan PMK, Hosur R V. NMR elucidation of early folding hierarchy in HIV-1 protease. J. Biol. Chem. 2003;278:19980–19985.
33. Rout MK, Hosur R V. Fluctuating partially native-like topologies in the acid denatured ensemble of autolysis resistant HIV-1 protease. Arch. Biochem. Biophys. 2009;482:33–41.
34. Chatterjee A, Mridula P, Mishra RK, Mittal R, Hosur R V. Folding regulates autoprocessing of HIV-1 protease precursor. J. Biol. Chem. 2005;280:11369–11378.
35. Kay L, Keifer P, Saarinen T. Pure absorption gradient enhanced heteronuclear single quantum correlation spectroscopy with improved sensitivity. J. Am. Chem. Soc. 1992;114:10663–10665.
36. Kay LE, Ikura M, Tschudin R, Bax A. Three-dimensional triple-resonance NMR spectroscopy of isotopically enriched proteins. J. Magn. Reson. 1990;89:496–514.
37. Clubb RT, Thanabal V, G. Wagner. A constant-time three-dimensional triple-resonance pulse scheme to correlate intraresidue 1HN, 15N, and 13C’ chemical shifts in 15N—13C-labelled proteins. J. Magn. Reson. 1992;97:213–217.
38. Bax A, Ikura M. An efficient 3D NMR technique for correlating the proton and 15N backbone amide resonances with the alpha-carbon of the preceding residue in uniformly 15N/13C enriched proteins. J. Biomol. NMR. 1991;1:99–104.
39. Wittekind M, L. Mueller. HNCACB, a high-sensitivity 3D NMR experiment to correlate amide-proton and nitrogen resonances with the alpha- and beta-carbon resonances in proteins. J. Magn. Reson. Ser. B. 1993;101:201–205.
40. Grzesiek S, Bax A. Correlating backbone amide and side chain resonances in larger proteins by multiple relayed triple resonance NMR. J. Am. Chem. Soc. 1992;114:6291–6293.
41. Panchal SC, Bhavesh NS, V. Hosur R. Improved 3D triple resonance experiments, HNN and HN(C)N, for HN and 15N sequential correlations in (13C, 15N) labeled proteins: application to unfolded proteins. J. Biol. Chem. 2001;20:135–147.
42. Zhang O, Kay LE, Olivier JP, Forman-Kay JD. Backbone 1H and 15N resonance assignments of the N-terminal SH3 domain of drk in folded and unfolded states using enhanced-sensitivity pulsed field gradient NMR techniques. J. Biomol. NMR. 1994;4:845–858.
43. L. E. Kay, Torchia DA, Bax A. Backbone dynamics of proteins studied by 15N inverse-detected heteronuclar NMR spectroscopy: Application to staphylococcal nuclease. Biochemistry. 1989;28:8972–8979.
44. Balayssac S, Delsuc M-A, Gilard V, Prigent Y, Malet-Martino M. Two-dimensional DOSY experiment with Excitation Sculpting water suppression for the analysis of natural and biological media. J. Magn. Reson. 2009;196:78–83.
45. Wishart DS, Bigam CG, Yao J, Abildgaard F, Jane HD, Oldfield E, Markley JL, Sykes BD. Chemical shift referencing in biomolecular NMR. J. Biomol. NMR. 1995;6:135–140.
46. Delaglio F, Grzesiek S, Vuister GW, Zhu G, Pfeifer J, Bax a. NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J. Biomol. NMR. 1995;6:277–93.
47. Orekhov VY, Jaravine VA. Analysis of non-uniformly sampled spectra with multi-dimensional decomposition. Prog. Nucl. Magn. Reson. Spectrosc. 2011;59:271–92.
48. Vranken WF, Boucher W, Stevens TJ, Fogh RH, Pajon A, Llinas M, Ulrich EL, Markley JL, Ionides J, Laue ED. The CCPN data model for NMR spectroscopy: development of a software pipeline. Proteins. 2005;59:687–96.
49. D’Auvergne EJ, Gooley PR. Optimisation of NMR dynamic models I. Minimisation algorithms and their performance within the model-free and Brownian rotational diffusion spaces. J. Biomol. NMR. 2009;40:107–119.
50. D’Auvergne EJ, Gooley PR. Optimisation of NMR dynamic models II. A new methodology for the dual optimisation of the model-free parameters and the Brownian rotational diffusion tensor. J. Biomol. NMR. 2009;40:121–133.
51. Nilsson M. The DOSY Toolbox: a new tool for processing PFG NMR diffusion data. J. Magn. Reson. 2009;200:296–302.
52. MATLAB, The MathWorks, Inc.
53. Klein-Seetharaman J, Oikawa M, Grimshaw SB, Wirmer J, Duchardt E, Ueda T, Imoto T, Smith LJ, Dobson CM, Schwalbe H. Long-range interactions within a nonnative protein. Science. 2002;295:1719–1722.
54. Robustelli P, Piana S, Shaw DE. Developing a molecular dynamics force field for both folded and disordered protein states. Proc. Natl. Acad. Sci. U. S. A. 2018;115:E4758–E4766.
55. Páll S, Zhmurov A, Bauer P, Abraham M, Lundborg M, Gray A, Hess B, Lindahl E. Heterogeneous parallelization and acceleration of molecular dynamics simulations in GROMACS. J. Chem. Phys. 2020;153:134110.
56. Shen Y, Bax A. SPARTA+: a modest improvement in empirical NMR chemical shift prediction by means of an artificial neural network. J. Biomol. NMR. 2010;48:13–22.
57. Dagil R, Knudsen MJ, Olsen JG, O’Shea C, Franzmann M, Goffin V, Teilum K, Breinholt J, Kragelund BB. The WSXWS Motif in Cytokine Receptors Is a Molecular Switch Involved in Receptor Activation: Insight from Structures of the Prolactin Receptor. 2012;20:270–282.
58. Kogo H, Takeuchi K, Inoue H, Kihara H, Kojima M, Takahashi K. Urea-dependent unfolding of HIV-1 protease studied by circular dichroism and small-angle X-ray scattering. Biochim. Biophys. Acta. 2009;1794:70–74.
59. Todd MJ, Semo N, Freire E. The structural stability of the HIV-1 protease. J. Mol. Biol. 1998;283:475–488.
60. Levy Y, Caflisch A, Onuchic JN, Wolynes PG. The folding and dimerization of HIV-1 protease: evidence for a stable monomer from simulations. J. Mol. Biol. 2004;340:67–79.
61. Louis JM, Ishima R, Aniana A, Sayer JM. Revealing the dimer dissociation and existence of a folded monomer of the mature HIV-2 protease. Protein Sci. 2009;18:2442–53.
62. Schwalbe H, Fiebig KM, Buck M, Jones JA, Grimshaw SB, Spencer A, Glaser SJ, Smith LJ, Dobson CM. Structural and dynamical properties of a denatured protein. Heteronuclear 3D NMR experiments and theoretical simulations of lysozyme in 8 M urea. 1997;36:8977–8991.
63. Farrow N, Zhang O, Szabo A, Torchia D, Kay LE. Spectral density function mapping using 15N relaxation data exclusively. J. Biomol. NMR. 1995;6:153–62.
64. Nygaard M, Kragelund BB, Papaleo E, Lindorff-Larsen K. An Efficient Method for Estimating the Hydrodynamic Radius of Disordered Protein Conformations. Biophys. J. 2017;113:550–557.
65. Karplus M, Weaver DL. Protein-folding dynamics. Nature. 1976;260:404–406.
66. Broglia R, Tiana G. Hierarchy of events in the folding of model proteins. J. Chem. Phys. 2001;114:7267–7273.
67. Broglia RA, Tiana G, Pasquali S, Roman HE, Vigezzi E. Folding and aggregation of designed proteins. Proc. Natl. Acad. Sci. U. S. A. 1998;95:12930–12933.