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Title: The CC+ tool set : a web-based resource for studying coiled-coil bioinformatics
Author: Testa, Oliver David
ISNI:       0000 0004 2717 1838
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2011
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Coiled-coil motifs are elements of protein structure, which, whilst based on relatively simple sequences, form a variety of structures and perform various functions in biology. The subtleties in coiled-coil sequences that lead to this diversity are not yet comprehensively understood. This thesis aims to explore these relationships by putting in place of relational database of coiled-coil structures and sequences. To this end coiled-coil motifs were identified from the POB using the SOCKET algorithm. The identified assignments were collated and organized into the CC+ tool set, and this was used to study various contemporary issues in coiled-coil research. CC+ comprises an organized file system of data made during coiled-coil assignments, and a subset of these data was parsed into a relational database. The relational database facilitates searching coiled-coil data sets for motifs of specific topologies, configurations and composition. Using the tool set, compiling data sets of specific coiled-coil data is no longer a laborious manual undertaking, but a simple and speedy process conducted in real time. This process was further enhanced with the implementation of an on-line interface; the web site facilitates interrogation of the tool set, visualization of the coiled-coil assignments returned from the database, and exporting data for further study elsewhere. The tool set was used to study several aspects of coiled-coil sequence-to-structure relationships. Searches performed on amino-acid interactions occurring within the hydrophobic interface of antiparallel, 2-helix coiled coils yielded hypotheses consistent with the findings of an independent experimental system. Networks of polar interactions incorporating as- paragine and an ion ligand within the hydrophobia interface of 3-helix coiled coils have also been observed and studied. Throughout these studies, it was apparent that many coiled-coil assignments within the tool set are either exact duplicates, or redundant due to the highly repetitive nature of identified coiled-coil sequences. Therefore, algorithms were developed to determine the relative redundancies of different aspect of coiled-coil structure, and these are incorporated dynamically into web-based searching to improve the quality of the data sets returned. Numerous algorithms exist to predict the formation of coiled-coil structure using amino-acid sequences, and these are based on specific amino-acid compositions recorded from manually compiled data sets. It is hoped that the CC+ tool set will facilitate refinement of existing coiled-coil prediction algorithms by contributing updated data sets, and even contribute in the creation of more accurate prediction methods in future. Furthermore, specific amino- acid interactions within coiled-coil systems have been investigated, and conclusions made regarding their effect on coiled-coil stability, illustrating the tool set's potential in facilitating de novo design of novel coiled-coil interactions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available