@phdthesis{Weikl2007,
  author    = {Weikl, Thomas R.},
  title     = {Transition states and loop-closure principles in protein folding},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-26975},
  school      = {Universit{\"a}t Potsdam},
  year      = {2007},
  abstract  = {Proteins are chain molecules built from amino acids. The precise sequence of the 20 different types of amino acids in a protein chain defines into which structure a protein folds, and the three-dimensional structure in turn specifies the biological function of the protein. The reliable folding of proteins is a prerequisite for their robust function. Misfolding can lead to protein aggregates that cause severe diseases, such as Alzheimer's, Parkinson's, or the variant Creutzfeldt-Jakob disease. Small single-domain proteins often fold without experimentally detectable metastable intermediate states. The folding dynamics of these proteins is thought to be governed by a single transition-state barrier between the unfolded and the folded state. The transition state is highly instable and cannot be observed directly. However, mutations in which a single amino acid of the protein is substituted by another one can provide indirect access. The mutations slightly change the transition-state barrier and, thus, the folding and unfolding times of the protein. The central question is how to reconstruct the transition state from the observed changes in folding times. In this habilitation thesis, a novel method to extract structural information on transition states from mutational data is presented. The method is based on (i) the cooperativity of structural elements such as alpha-helices and beta-hairpins, and (ii) on splitting up mutation-induced free-energy changes into components for these elements. By fitting few parameters, the method reveals the degree of structure formation of alpha-helices and beta-hairpins in the transition state. In addition, it is shown in this thesis that the folding routes of small single-domain proteins are dominated by loop-closure dependencies between the structural elements.},
  language  = {en}
}
@phdthesis{Weikl1999,
  author    = {Weikl, Thomas R.},
  title     = {Adh{\"a}sion von mehrkomponentigen Membranen},
  address   = {Potsdam},
  pages     = {110 S. : graph. Darst.},
  year      = {1999},
  language  = {de}
}
@article{ReichBeckerSeckleretal.2009,
  author    = {Reich, Lothar and Becker, Marion and Seckler, Robert and Weikl, Thomas R.},
  title     = {In vivo folding efficiencies for mutants of the P22 tailspike beta-helix protein correlate with predicted stability changes},
  issn      = {0301-4622},
  doi       = {10.1016/j.bpc.2009.01.015},
  year      = {2009},
  abstract  = {Parallel A-helices are among the simplest repetitive structural elements in proteins. The folding behavior of A- helix proteins has been studied intensively, also to gain insight on the formation of amyloid fibrils, which share the parallel beta-helix as a central structural motif. An important system for investigating beta-helix folding is the tailspike protein from the Salmonella bacteriophage P22. The central domain of this protein is a right-handed parallel beta-helix with 13 windings. Extensive mutational analyses of the P22 tailspike protein have revealed two main phenotypes: temperature-sensitive-folding (tsf) mutations that reduce the folding efficiency at elevated temperatures, and global suppressor (su) mutations that increase the tailspike folding efficiency. A central question is whether these phenotypes can be understood from changes in the protein stability induced by the mutations. Experimental determination of the protein stability is complicated by the nearly irreversible trimerization of the folded tailspike protein. Here, we present calculations of stability changes with the program FoldX, focusing on a recently published extensive data set of 145 singe-residue alanine mutants. We find that the calculated stability changes are correlated with the experimentally measured in vivo folding efficiencies. In addition, we determine the free-energy landscape of the P22 tailspike protein in a nucleation-propagation model to explore the folding mechanism of this protein, and obtain a processive folding route on which the protein nucleates in the N-terminal region of the helix.},
  language  = {en}
}
@article{RaatzWeikl2017,
  author    = {Raatz, Michael and Weikl, Thomas R.},
  title     = {Membrane Tubulation by Elongated and Patchy Nanoparticles},
  series = {Advanced materials interfaces},
  volume    = {4},
  journal   = {Advanced materials interfaces},
  number    = {1},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {2196-7350},
  doi       = {10.1002/admi.201600325},
  pages     = {8},
  year      = {2017},
  abstract  = {Advances in nanotechnology lead to an increasing interest in how nanoparticles interact with biomembranes. Nanoparticles are wrapped spontaneously by biomembranes if the adhesive interactions between the particles and membranes compensate for the cost of membrane bending. In the last years, the cooperative wrapping of spherical nanoparticles in membrane tubules has been observed in experiments and simulations. For spherical nanoparticles, the stability of the particle-filled membrane tubules strongly depends on the range of the adhesive particle-membrane interactions. In this article, it is shown via modeling and energy minimization that elongated and patchy particles are wrapped cooperatively in membrane tubules that are highly stable for all ranges of the particle-membrane interactions, compared to individual wrapping of the particles. The cooperative wrapping of linear chains of elongated or patchy particles in membrane tubules may thus provide an efficient route to induce membrane tubulation, or to store such particles in membranes.},
  language  = {en}
}