Valdar, William Seth Jermy;
(2001)
Residue conservation in the prediction of protein-protein interfaces.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Evolutionary information derived from the large number of available protein sequences and structures could powerfully guide both analysis and prediction of protein-protein interfaces. Three questions are addressed. First, can residue conservation be quantified? Second, are protein-protein interfaces conserved? Third, can the conservation of protein-protein interfaces be useful in their prediction? To answer the first question, this work reviews 17 methods to quantify positional residue conservation in multiple alignments. It proposes two new measures: one a concrete score, which is then used throughout the remainder of the work, and the other a generalized formula for scoring conservation. To answer the second question, the conservation of residues at protein-protein interfaces is compared with other residues on the protein surface in six homodimer families. A probabilistic evaluation shows that interface conservation is higher than expected by chance and usually statistically significant at the 5% level or better. To answer the third question, the utility of conservation in the discrimination of biological from non-biological crystal contacts is assessed. Conservation and size information is calculated for contacts in 53 families of homodimers and 65 families of monomers. Biological contacts are shown to be usually conserved and typically the largest contact in the crystal. Neural networks are then applied to the problem of using size and conservation alone or in combination to predict whether or not a given contact is biologically relevant. The best neural networks combine the two measures and achieve accuracies of over 98%. It is concluded that although size is the most powerful single discriminant, conservation adds important predictive value.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Residue conservation in the prediction of protein-protein interfaces |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| Keywords: | Pure sciences; Biological sciences; Residue conservation |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10097808 |
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