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High-Resolution Free-Energy Landscape Analysis of α-Helical Protein Folding: HP35 and Its Double Mutant.

Banushkina PV, Krivov SV - J Chem Theory Comput (2013)

Bottom Line: Natl.Four different estimations of the pre-exponential factor for both proteins give k 0 (-1) values of approximately a few tens of nanoseconds.Our analysis gives detailed information about folding of the proteins and can serve as a rigorous common language for extensive comparison between experiment and simulation.

View Article: PubMed Central - PubMed

Affiliation: Astbury Center for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds , Leeds LS2 9JT, United Kingdom.

ABSTRACT
The free-energy landscape can provide a quantitative description of folding dynamics, if determined as a function of an optimally chosen reaction coordinate. Here, we construct the optimal coordinate and the associated free-energy profile for all-helical proteins HP35 and its norleucine (Nle/Nle) double mutant, based on realistic equilibrium folding simulations [Piana et al. Proc. Natl. Acad. Sci. U.S.A. 2012, 109, 17845]. From the obtained profiles, we directly determine such basic properties of folding dynamics as the configurations of the minima and transition states (TS), the formation of secondary structure and hydrophobic core during the folding process, the value of the pre-exponential factor and its relation to the transition path times, the relation between the autocorrelation times in TS and minima. We also present an investigation of the accuracy of the pre-exponential factor estimation based on the transition-path times. Four different estimations of the pre-exponential factor for both proteins give k 0 (-1) values of approximately a few tens of nanoseconds. Our analysis gives detailed information about folding of the proteins and can serve as a rigorous common language for extensive comparison between experiment and simulation.

No MeSH data available.


Related in: MedlinePlus

Free-energy profile forwild-type villin (HP35) along the putativeoptimal reaction coordinate. [Legend: D, the denatured basin; I, theintermediate basin; N, the native basin; TS1, the first transitionstate; and TS2 the second transition state.] The main folding barrierbetween D and I states is ΔF/kBT ≈ 5.5. The representative structuresfor the regions of the landscape show a trajectory snapshot closestto the average structure of the region. Colors code the root-mean-square(rms) fluctuations of atomic positions around the average structurefrom 1.5 Å (blue) to 7 Å (red).
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fig1: Free-energy profile forwild-type villin (HP35) along the putativeoptimal reaction coordinate. [Legend: D, the denatured basin; I, theintermediate basin; N, the native basin; TS1, the first transitionstate; and TS2 the second transition state.] The main folding barrierbetween D and I states is ΔF/kBT ≈ 5.5. The representative structuresfor the regions of the landscape show a trajectory snapshot closestto the average structure of the region. Colors code the root-mean-square(rms) fluctuations of atomic positions around the average structurefrom 1.5 Å (blue) to 7 Å (red).

Mentions: Figure 1 shows the FEP of wild-type villinHP35 as a functionof the determined reaction coordinate. The landscape consists of fivestates: denatured basin (D), first transition state (TS1), intermediatestate (I), second transition state (TS2), and native basin (N). Themain folding barrier is the one between the denatured and intermediatestates, with the height of ΔF/kBT ≈ 5.5.


High-Resolution Free-Energy Landscape Analysis of α-Helical Protein Folding: HP35 and Its Double Mutant.

Banushkina PV, Krivov SV - J Chem Theory Comput (2013)

Free-energy profile forwild-type villin (HP35) along the putativeoptimal reaction coordinate. [Legend: D, the denatured basin; I, theintermediate basin; N, the native basin; TS1, the first transitionstate; and TS2 the second transition state.] The main folding barrierbetween D and I states is ΔF/kBT ≈ 5.5. The representative structuresfor the regions of the landscape show a trajectory snapshot closestto the average structure of the region. Colors code the root-mean-square(rms) fluctuations of atomic positions around the average structurefrom 1.5 Å (blue) to 7 Å (red).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3860327&req=5

fig1: Free-energy profile forwild-type villin (HP35) along the putativeoptimal reaction coordinate. [Legend: D, the denatured basin; I, theintermediate basin; N, the native basin; TS1, the first transitionstate; and TS2 the second transition state.] The main folding barrierbetween D and I states is ΔF/kBT ≈ 5.5. The representative structuresfor the regions of the landscape show a trajectory snapshot closestto the average structure of the region. Colors code the root-mean-square(rms) fluctuations of atomic positions around the average structurefrom 1.5 Å (blue) to 7 Å (red).
Mentions: Figure 1 shows the FEP of wild-type villinHP35 as a functionof the determined reaction coordinate. The landscape consists of fivestates: denatured basin (D), first transition state (TS1), intermediatestate (I), second transition state (TS2), and native basin (N). Themain folding barrier is the one between the denatured and intermediatestates, with the height of ΔF/kBT ≈ 5.5.

Bottom Line: Natl.Four different estimations of the pre-exponential factor for both proteins give k 0 (-1) values of approximately a few tens of nanoseconds.Our analysis gives detailed information about folding of the proteins and can serve as a rigorous common language for extensive comparison between experiment and simulation.

View Article: PubMed Central - PubMed

Affiliation: Astbury Center for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds , Leeds LS2 9JT, United Kingdom.

ABSTRACT
The free-energy landscape can provide a quantitative description of folding dynamics, if determined as a function of an optimally chosen reaction coordinate. Here, we construct the optimal coordinate and the associated free-energy profile for all-helical proteins HP35 and its norleucine (Nle/Nle) double mutant, based on realistic equilibrium folding simulations [Piana et al. Proc. Natl. Acad. Sci. U.S.A. 2012, 109, 17845]. From the obtained profiles, we directly determine such basic properties of folding dynamics as the configurations of the minima and transition states (TS), the formation of secondary structure and hydrophobic core during the folding process, the value of the pre-exponential factor and its relation to the transition path times, the relation between the autocorrelation times in TS and minima. We also present an investigation of the accuracy of the pre-exponential factor estimation based on the transition-path times. Four different estimations of the pre-exponential factor for both proteins give k 0 (-1) values of approximately a few tens of nanoseconds. Our analysis gives detailed information about folding of the proteins and can serve as a rigorous common language for extensive comparison between experiment and simulation.

No MeSH data available.


Related in: MedlinePlus