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Explicit Characterization of the Free-Energy Landscape of a Protein in the Space of All Its C
- Source :
- Journal of chemical theory and computation. 16(1)
- Publication Year :
- 2019
-
Abstract
- By using an approach that allows computing the free energy in high-dimensional spaces together with a clustering technique capable of identifying kinetic attractors stabilized by conformational disorder, we analyze a molecular dynamics trajectory of the Villin headpiece from Lindorff-Larsen, K.; et al. How fast-folding proteins fold. Science 2011, 334, 517-520. We compute its free-energy landscape in the space of all its Cα carbons. This landscape has the shape of a 12-dimensional funnel with the free energy decreasing monotonically as a function of the native contacts. There are no significant folding barriers. The funnel can be partitioned in five regions, three mainly folded and two unfolded, which behave as Markov states. The slowest relaxation time among these states corresponds to the folding transition. The second slowest time is only twice smaller and corresponds to a transition within the unfolded state. This indicates that the unfolded part of the funnel has a nontrivial shape, which induces a sizable kinetic barrier between disordered states.
- Subjects :
- Animals
Carbon
Chickens
Cluster Analysis
Kinetics
Markov Chains
Microfilament Proteins
Molecular Dynamics Simulation
Protein Conformation
Protein Folding
Thermodynamics
Space (mathematics)
Kinetic energy
01 natural sciences
Settore FIS/03 - Fisica della Materia
Molecular dynamics
Protein structure
0103 physical sciences
Attractor
Physical and Theoretical Chemistry
Cluster analysis
Physics
Kinetic
Cluster Analysi
010304 chemical physics
Animal
Energy landscape
Markov Chain
Microfilament Protein
Chicken
Computer Science Applications
Protein folding
Biological system
Subjects
Details
- ISSN :
- 15499626
- Volume :
- 16
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of chemical theory and computation
- Accession number :
- edsair.doi.dedup.....0455e62067ddacf94a44692ed7932e65