Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360133
Title: Hydrogen bonding and the stability of the polypeptide backbone
Author: Maccallum, Peter Hugh
ISNI:       0000 0001 3614 8670
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1996
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Abstract:
The tertiary structures of globular proteins are crucial in determining reactivity and specificity as biological catalysts and signalling systems. The rules determining the final fold of a protein are still unknown, but some progress has been made in defining tertiary structure in terms of the secondary structure, the conformation of the polypeptide chain. Perhaps surprisingly, not all of the conformational properties of this backbone are known, and several new approaches to studying these are described. Most studies of peptide structure have focused on hydrogen bonding, and this is used as a starting point for this study. Different descriptions of the hydrogen bond, from geometric rules to ab initio calculations, are considered, and an approach based on analysing contributions of individual polar groups to the potential energy using semi empirical Lennard-Jones calculations is chosen on grounds of accuracy, flexibility, and ease of calculation. Using this approach, it is shown that electrostatic interactions between main chain atoms stabilise the right handed twist found in Beta-strands and similar interactions between main-chain atoms not hydrogen bonded to each other influence the geometries of hydrogen bonds in Alpha-helices and Beta-sheets. A role for water and tertiary hydrogen bonds in determining backbone conformation is suggested. The same technique makes it possible to investigate interatomic repulsions as well as attractions. A detailed analysis of the attractions and repulsions in an idealised polypeptide explains many of the features of helical structures in proteins, and suggests a hitherto unexpected directional helix forming pathway, which is supported by a range of kinetic and structural data. Software for automated searching of a hydrogen bond database is developed, and used to identify hydrogen bonded rings formed by amide side chains and main chain peptides. Integrating the database with novel visualisation techniques allows a previously unidentified property of beta sheets, the hydrophobic ridge, to be detected. A range of different computational approaches was used surging this research, from molecular modelling to database searching. Several pieces of software were developed, and these are described together with some observations about the types of software and working environments which were found to be useful in structural biochemistry, and what types of software technology could be developed to make this task easier.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.360133  DOI: Not available
Keywords: Proteins; Biomolecular structure
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