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A syntactic approach to protein topology prediction

Hatrick, Kerr; (1994) A syntactic approach to protein topology prediction. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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The structure any particular part of a protein adopts is determined by the sequence itself and the surrounding context or chemical environment. The correct prediction of protein structure at any particular position in the sequence therefore requires a component relating the context of the position to the sequence at that position. In this thesis we formalize the embedding of context in protein grammars which describe the arrangement of structural features in protein families; we also develop an algorithm to recognize these grammars. This algorithm requires substantial extension of classical syntactic analysis to cope with the problem of overlapping tokens. Development of new methods to rank grammatical paths and evaluate semantic predicates was also necessary. The interaction of context and sequence is manifest in the type of mutations that occur at a particular point in a multiple sequence alignment; in particular, whether changes that occur there are related to changes elsewhere in the multiple alignment. Such changes are referred to as coordinated changes; a method was devised to recognise these changes at positions in protein multiple sequence alignments using different models of amino acid relatedness. The method had been designed to bypass the limitations of previous methods based on simple pattern matching. We discuss the implications of the ability to harness contextual information from evolutionary, folding and comparative structural analysis for topology prediction.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: A syntactic approach to protein topology prediction
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Protein grammars
URI: https://discovery.ucl.ac.uk/id/eprint/10108389
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