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Temperature evolution of Trp-cage folding pathways: An analysis by dividing the probability flux field into stream tubes
- Source :
- Journal of Biological Physics. 43:565-583
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Owing to its small size and very fast folding rate, the Trp-cage miniprotein has become a benchmark system to study protein folding. Two folding pathways were found to be characteristic of this protein: pathway I, in which the hydrophobic collapse precedes the formation of α-helix, and pathway II, in which the events occur in the reverse order. At the same time, the relative contribution of these pathways at different temperatures as well as the nature of transition from one pathway to the other remain unclear. To gain insight into this issue, we employ a recently proposed hydrodynamic description of protein folding, in which the process of folding is considered as a motion of a “folding fluid” (Chekmarev et al., Phys. Rev. Lett. 100(1), 018107 2008). Using molecular dynamics simulations, we determine the field of probability fluxes of transitions in a space of collective variables and divide it into stream tubes. Each tube contains a definite fraction of the total folding flow and can be associated with a certain pathway. Specifically, three temperatures were considered, T = 285K, T = 315K, and T = 325K. We have found that as the temperature increases, the contribution of pathway I, which is approximately 90% of the total folding flow at T = 285K, decreases to approximately 10% at T = 325K, i.e., pathway II becomes dominant. At T = 315K, both pathways contribute approximately equally. All these temperatures are found below the calculated melting point, which suggests that the Trp-cage folding mechanism is determined by kinetic factors rather than thermodynamics.
- Subjects :
- Protein Folding
Protein Conformation
Biophysics
Thermodynamics
Molecular Dynamics Simulation
010402 general chemistry
01 natural sciences
Molecular dynamics
Protein structure
0103 physical sciences
Amino Acid Sequence
Hydrophobic collapse
Molecular Biology
Original Paper
010304 chemical physics
Chemistry
Temperature
Tryptophan
Proteins
Cell Biology
Contact order
Atomic and Molecular Physics, and Optics
0104 chemical sciences
Folding (chemistry)
Melting point
Protein folding
Downhill folding
Subjects
Details
- ISSN :
- 15730689 and 00920606
- Volume :
- 43
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Physics
- Accession number :
- edsair.doi.dedup.....53b3f48c09bb0fef6f774467c596f7f5