Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599025
Title: Inverse protein folding, hierarchical optimisation and tie knots
Author: Fink, T. M. A.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1998
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Abstract:
This dissertation is composed of three parts: inverse protein folding, hierarchical optimisation and tie knots. Chapters 2 - 7 describe inverse folding, the design of proteins which quickly and stably fold to specified target conformations. In Chapters 8 - 10 we introduce hierarchical optimisation, a generalisation of conventional optimisation in which the solution must be determined stage-wise in light of successive information learnt. We provide a mathematical model of necktie knots in Chapter 11, with the express intention of recovering the traditional, and predicting new, aesthetic tie knots. We review in Chapter 2 the development of protein folding and design, which has occurred almost entirely during the last four decades. Central to recent theoretical advances are the conformational energy landscape and lattice models of proteins. We present the statistical mechanical interpretation of protein folding afforded by the energy landscape picture and consider its topographic structure. Landscapes associated with the kinetic and free energy barriers impeding stable, fast folding are identified and serve to indicate ideal protein landscapes. In Chapter 3 we first examine lattice models of proteins, which contain the fundamental attributes of proteins in the absence of biological periphery. We describe lattice folding dynamics and introduce an analytic representation of lattic proteins, both of which are used extensively throughout this dissertation. We then review thermodynamically oriented sequence selection, an important method of protein design for lattice proteins. Sequences made to be thermodynamically stable in a desired target conformation are observed in simulation to fold more quickly to the target as well. In Chapter 4 we characterise protein folding by thermodynamic stability and kinetic accessibility of the native state, which are the benchmarks of a sequence determined by successful design. The relationship between folding speed and stability is captured by the accessibility-stability phase space. These qualities, observed through folding simulation to be correlated in Chapter 3, are shown to be in conflict near the extremes of either. It is demonstrated, in particular, that thermodynamically oriented sequence selection does not favour optimal accessibility.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.599025  DOI: Not available
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