Nanoscale Brownian Dynamics of Semiflexible Biopolymers

Mühle, Steffen

dc.contributor.advisor	Enderlein, Jörg Prof. Dr.
dc.contributor.author	Mühle, Steffen
dc.date.accessioned	2020-07-24T11:36:02Z
dc.date.available	2020-07-24T11:36:02Z
dc.date.issued	2020-07-24
dc.identifier.uri	http://hdl.handle.net/21.11130/00-1735-0000-0005-1433-B
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-8127
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc	571.4	de
dc.title	Nanoscale Brownian Dynamics of Semiflexible Biopolymers	de
dc.type	doctoralThesis	de
dc.contributor.referee	Enderlein, Jörg Prof. Dr.
dc.date.examination	2020-07-16
dc.description.abstracteng	Proteins are one of, if not the most, versatile of biology’s tools, performing a great variety of functions in living organisms and giving rise to behavior as complex as life itself. They are linear chains of amino acids and therefore heteropolymers from a chemical point of view. Performing diverse tasks while obeying the laws of thermodynamics and microscopic physics, proteins thus invoke the interest of biologists, chemists and physicists alike. While the theoretical foundations for describing molecular motion can be traced back more than a century, experimental techniques allowing us to measure the dynamics of single molecules have only become available in the last twenty years. Here, we aim to link the two together and use data from single-molecule experiments to infer characteristic properties of individual proteins in a systematic and quantitative manner. In particular, we have at our disposal three complementing methods which measure dynamical properties of single molecules. The first is photo-induced electron transfer paired with fluorescence correlation spectroscopy (PET-FCS) which measures their end-to-end or internal-to-end loop formation rate, the second is dual-focus fluorescence correlation spectroscopy (2fFCS) which measures their hydrodynamic radius, and the third is dynamic metal-induced energy transfer (dynaMIET) which measures their reconfiguration time when bound to a surface. In this thesis, we develop a polymer model which enables the efficient interpretation of results from PET-FCS, 2fFCS and dynaMIET experiments. This model is a bead-rod chain which takes into account hydrodynamic interactions, excluded volume effects, bending rigidity and the fluorophore with which the protein is labeled, while including only two free parameters. It quantitatively reproduces systematically measured data from PET-FCS and 2fFCS applied to glycine-serine (GS) repeats – the prototype of an intrinsically disordered protein (IDP). Loop formation dynamics in GS-repeats typically take tens of nanoseconds, and their hydrodynamic radius is around one nanometer. From this data, the model yields a persistence length of lP = 5.2+- Å and one amino acid’s hydrodynamic radius of a = 3.5 +- 0.7 Å, while at the same time validating the important role of excluded volume effects in the dynamics of GS-repeats. Thus, we now have at hand a combined method of performing single-molecule experiments and Brownian dynamics simulations for IDPs which yields quantitative insights into their molecular properties. This enables further study of the elastic and hydrodynamic properties associated with different amino acid sequences. Extending the model to take into account secondary structures, inhomogeneities or internal friction effects should be subject to future work. This may improve our understanding of the mechanisms governing protein function and folding, and hence contribute to novel medical treatments and drug design.	de
dc.contributor.coReferee	Wardetzky, Max Prof. Dr.
dc.subject.eng	complex systems	de
dc.subject.eng	polymer dynamics	de
dc.subject.eng	brownian motion	de
dc.subject.eng	elasticity	de
dc.subject.eng	differential geometry	de
dc.subject.eng	single-molecule experiment	de
dc.subject.eng	single-molecule experiments	de
dc.subject.eng	biophysics	de
dc.subject.eng	fluorescence correlation spectroscopy	de
dc.subject.eng	loop formation	de
dc.subject.eng	translational diffusion	de
dc.subject.eng	stochastic dynamics	de
dc.subject.eng	thermal equilibrium	de
dc.subject.eng	overdamped hydrodynamics	de
dc.subject.eng	conformational dynamics	de
dc.subject.eng	protein dynamics	de
dc.subject.eng	protein folding	de
dc.subject.eng	loop closure kinetics	de
dc.subject.eng	intrinsically disordered protein	de
dc.subject.eng	PET-FCS	de
dc.subject.eng	2fFCS	de
dc.subject.eng	hydrodynamic radius	de
dc.identifier.urn	urn:nbn:de:gbv:7-21.11130/00-1735-0000-0005-1433-B-5
dc.affiliation.institute	Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)	de
dc.subject.gokfull	Biologie (PPN619462639)	de
dc.identifier.ppn	1725539012

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GGNB - Göttinger Graduiertenzentrum für Neurowissenschaften, Biophysik und molekulare Biowissenschaften [1112]
GGNB - Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences

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