Prediction and analysis of protein structure
MetadataShow full item record
This thesis, which contains an introduction and four manuscripts, summarises my efforts during my the past four years to understand proteins, their structure and dynamics. The first manuscript presents a protocol that refines models as part of a protein structure prediction pipeline. To achieve this, we used spatial information from determined structures and sequence information from multiple alignments. The protocol was used to improve the quality of rough models containing only one point per residue. In the second manuscript we investigated protein fold space. We compared models with known fold to determined structures and found that out models contained many folds that were not seen in the present pool of structures in the PDB. Comparison of structural features revealed no reason why the model folds could not exist. We investigated how well geometric comparison methods distinguished fold in the third manuscript. We presented a novel measure of topological similarity and showed that geometric methods have trouble distinguishing fold differences between both models and PDB structures. In the last manuscript we showed that the architecture is the most important factor for dynamics as measured by normal modes. Protein fold has some effect and cannot be discarded completely, but larger differences in fold does not necessarily correspond to larger differences in flexibility if the architecture is the same.
Paper I: Protein and Peptide Letters 15(9), Hollup, S. M.; Taylor, W. R.; Jonassen, I., Structural Fragments in Protein Model Refinement, pp. 964-971. Copyright 2008 Bentham Science Publishers. Full text not available in BORA due to publisher restrictions. The published version is available at: http://dx.doi.org/10.2174/092986608785849263Paper II: Structure 17(9), Taylor, W. R.; Chelliah, V.; Hollup, S. M.; MacDonald, J. T.; Jonassen, I., Probing the “Dark Matter” of Protein Fold Space, pp. 1244-1252. Copyright 2009 Elsevier. Full text not available in BORA due to publisher restrictions. The published version is available at: http://dx.doi.org/10.1016/j.str.2009.07.012Paper III: Hollup, S. M.; Sadowski, M. I.; Jonassen, I.; Taylor, W. R., 2010, Protein Fold Discrimination: an Evaluation of Geometric and Topology Based Measures. Full text not available in BORA. Part of it has been published in: Computational Biology and Chemistry 35(3), Hollup, S. M.; Sadowski, M. I.; Jonassen, I.; Taylor, W. R., Exploring the limits of fold discrimination by structural alignment: A large scale benchmark using decoys of known fold, pp. 174-188. The published version is available at: http://dx.doi.org/10.1016/j.compbiolchem.2011.04.008Paper IV: Protein Science 20(1), Hollup, S. M.; Fuglebakk, E.; Taylor, W. R.; Reuter, N., Exploring the factors determining the dynamics of different protein folds, pp. 197-209. Copyright 2010 The Protein Society. Published by Wiley-Blackwell. Full text not available in BORA due to publisher restrictions. The published version is available at: http://dx.doi.org/10.1002/pro.558