Internal Friction in Peptide Kinetics
Schulz, Julius Christoph Friedrich

HaupttitelInternal Friction in Peptide Kinetics
TitelvarianteInterne Reibung der Peptidkinetik
AutorSchulz, Julius Christoph Friedrich
Geburtsort: Berlin
GutachterProf. Dr. Roland R. Netz
weitere GutachterProf. Dr. Frank Noé
Freie Schlagwörterinternal friction; peptide; molecular dynamics
DDC572 Biochemie
530 Physik
ZusammenfassungProtein dynamics are significantly influenced by frictional effects, not only from the surrounding solvent but also due to interactions inside the protein chain itself. Experimentally, such “internal friction” has been investigated by studying folding or binding kinetics at varying solvent viscosity; however the molecular origin of these effects is hard to pinpoint. In this thesis, we studied the effects of internal friction by both equilbrium and non-equilibrium molecular dynamics simulations.
We developed a mechanism using scaled solvent mass to probe more than two orders of magnitude in viscosity without altering the free energy landscape of the protein. Our method is especially suited to investigate peptide kinetics near vanishing viscosities that are not reachable experimentally. While previous experimental studies have suggested different functional forms for the viscosity dependence, our findings suggest that solvent and internal friction effects are intrinsically entangled. This finding is rationalized by calculation of the polymer end-to-end distance dynamics from a Rouse model that includes internal friction. While this simple Rouse model does not include effects such as hydrogend bonds, an analysis of the local friction profile along different reaction coordinates suggests a connection between friction and the formation of hydrogen bonds upon folding.
Since hydrogen bonding is a major factor for the determination of secondary struc- ture, internal friction can help in understanding the folding process. As the secondary structure is of vast importance for the biological function of a protein, misfolding is thought to be the explanation for many diseases including neurogedegenerative ones such as Huntington’s or Parkinon’s disease. By the forced unfolding of polyglutamine and polyalanine homopeptides in competing α-helix and β-hairpin secondary structures, we disentangle equilibrium free-energetics from non-equilibrium dissipative ef- fects. We find that α-helices are characterized by larger friction or dissipation upon unfolding, regardless of whether they are free-energetically preferred over β-hairpins or not. Our analysis, based on MD simulations for atomistic peptide models with explicit water, suggests that this difference is related to the internal friction and mostly caused by the different characteristic number of intra-peptide hydrogen bonds in the α-helix and β-hairpin states, which is higher for the α-helical state.
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Seitenzahliv, 89 Seiten
Fachbereich/EinrichtungFB Physik
Rechte Nutzungsbedingungen
Tag der Disputation10.09.2015
Erstellt am29.04.2016 - 12:43:54
Letzte Änderung19.05.2016 - 07:56:24
Statische URLhttp://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000101909