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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

Model potential with two barriers U2(x) (denoted by the blue dotted line) andthe free-energyprofile along the reaction coordinate determined from the trajectory(denoted by the red line).
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fig11: Model potential with two barriers U2(x) (denoted by the blue dotted line) andthe free-energyprofile along the reaction coordinate determined from the trajectory(denoted by the red line).

Mentions: Model system 2 has an additional barrier in the “native”state with the following potential energy profile for x ∈ [0,50] (Figure A2):The trajectory was generated analogous tothe above for 1.5 × 106 steps. Figure A2 shows the free-energy profile constructed using the generatedtrajectory.


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)

Model potential with two barriers U2(x) (denoted by the blue dotted line) andthe free-energyprofile along the reaction coordinate determined from the trajectory(denoted by the red line).
© Copyright Policy
Related In: Results  -  Collection

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

fig11: Model potential with two barriers U2(x) (denoted by the blue dotted line) andthe free-energyprofile along the reaction coordinate determined from the trajectory(denoted by the red line).
Mentions: Model system 2 has an additional barrier in the “native”state with the following potential energy profile for x ∈ [0,50] (Figure A2):The trajectory was generated analogous tothe above for 1.5 × 106 steps. Figure A2 shows the free-energy profile constructed using the generatedtrajectory.

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