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Folding thermodynamics of a model three-helix-bundle protein - PubMed

  • ️Wed Jan 01 1997

Folding thermodynamics of a model three-helix-bundle protein

Y Zhou et al. Proc Natl Acad Sci U S A. 1997.

Abstract

The calculated folding thermodynamics of a simple off-lattice three-helix-bundle protein model under equilibrium conditions shows the experimentally observed protein transitions: a collapse transition, a disordered-to-ordered globule transition, a globule to native-state transition, and the transition from the active native state to a frozen inactive state. The cooperativity and physical origin of the various transitions are explored with a single "optimization" parameter and characterized with the Lindemann criterion for liquid versus solid-state dynamics. Below the folding temperature, the model has a simple free energy surface with a single basin near the native state; the surface is similar to that calculated from a simulation of the same three-helix-bundle protein with an all-atom representation [Boczko, E. M. & Brooks III, C. L. (1995) Science 269, 393-396].

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Figures

Figure 1
Figure 1

(Left) The three-helix-bundle protein [residues 10–55 of the B domain of Staphylococcus aureus protein A (Protein Data Base accession no. 1bdd) (6)]; the same 46 residue protein was used in ref. . (Right) The global energy-minimum structure for the model. [Drawn with

molscript

(9).]

Figure 2
Figure 2

The reduced heat capacity, Cv* (= Cv/kB) and the reduced squared radius of gyration per bead, Rg2/σc2N, as a function of temperatures. The lines in Cv* curves are obtained from the weighted histogram method (10, 15). The lines in Rg2 (dashed line, g = 1.3; solid line, g = 0.3) are from a spline fit. Error bars are less than the size of points excepted as shown.

Figure 3
Figure 3

Phase diagram of the three-helix-bundle protein along with the structures for g = 0.3 (Left) and g = 1.3 (Right) at selected temperatures. Four transitions (open circles connected by solid lines) are found from the peaks in the heat capacity. The collapse transition (open squares connected with dotted lines) was determined from the temperature at which dRg2/dT, the temperature derivative of the squared radius of gyration, is a maximum (see Fig. 2). All lines are drawn to serve as a guide. The first-order-like two-state transitions are indicated by a solid diamond. The structures shown for disordered globules and random coils are typical instantaneous structures and the structures for ordered globules and surface-molten solid are average structures; the average structures are obtained by averaging over 0.2–2 million configurations after removing translational and rotational motions by minimizing rms deviations with respect to the first configuration. [Drawn with

molscript

(9).]

Figure 4
Figure 4

Reduced free-energy landscape A* (A* = A/ɛ) at T* = 0.25 (the surface-molten-solid phase) for g = 0.3 and g = 0.7, as a function of the fraction of global-minimum contacts Q. The results were obtained with the weighted histogram method (10, 15). The larger gap model has a smoother landscape. There is a small free-energy barrier for g = 0.3 at Q ≈ 0.87; it yields a weakly bimodal potential energy distribution at the transition temperature (data not shown).

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