Development of genetic algorithm for optimisation of predicted membrane protein structures

2.50
Hdl Handle:
http://hdl.handle.net/10547/610599
Title:
Development of genetic algorithm for optimisation of predicted membrane protein structures
Authors:
Minaji-Moghaddam, Noushin
Abstract:
Due to the inherent problems with their structural elucidation in the laboratory, the computational prediction of membrane protein structure is an essential step toward understanding the function of these leading targets for drug discovery. In this work, the development of a genetic algorithm technique is described that is able to generate predictive 3D structures of membrane proteins in an ab initio fashion that possess high stability and similarity to the native structure. This is accomplished through optimisation of the distances between TM regions and the end-on rotation of each TM helix. The starting point for the genetic algorithm is from the model of general TM region arrangement predicted using the TMRelate program. From these approximate starting coordinates, the TMBuilder program is used to generate the helical backbone 3D coordinates. The amino acid side chains are constructed using the MaxSprout algorithm. The genetic algorithm is designed to represent a TM protein structure by encoding each alpha carbon atom starting position, the starting atom of the initial residue of each helix, and operates by manipulating these starting positions. To evaluate each predicted structure, the SwissPDBViewer software (incorporating the GROMOS force field software) is employed to calculate the free potential energy. For the first time, a GA has been successfully applied to the problem of predicting membrane protein structure. Comparison between newly predicted structures (tests) and the native structure (control) indicate that the developed GA approach represents an efficient and fast method for refinement of predicted TM protein structures. Further enhancement of the performance of the GA allows the TMGA system to generate predictive structures with comparable energetic stability and reasonable structural similarity to the native structure.
Citation:
Minaji-Moghaddam, N. (2007) 'Development of genetic algorithm for optimisation of predicted membrane protein structures'. PhD thesis. University of Bedfordshire.
Publisher:
University of Bedfordshire
Issue Date:
Mar-2007
URI:
http://hdl.handle.net/10547/610599
Type:
Thesis or dissertation
Language:
en
Appears in Collections:
PhD e-theses

Full metadata record

DC FieldValue Language
dc.contributor.authorMinaji-Moghaddam, Noushinen
dc.date.accessioned2016-05-24T08:27:05Zen
dc.date.available2016-05-24T08:27:05Zen
dc.date.issued2007-03en
dc.identifier.citationMinaji-Moghaddam, N. (2007) 'Development of genetic algorithm for optimisation of predicted membrane protein structures'. PhD thesis. University of Bedfordshire.en
dc.identifier.urihttp://hdl.handle.net/10547/610599en
dc.description.abstractDue to the inherent problems with their structural elucidation in the laboratory, the computational prediction of membrane protein structure is an essential step toward understanding the function of these leading targets for drug discovery. In this work, the development of a genetic algorithm technique is described that is able to generate predictive 3D structures of membrane proteins in an ab initio fashion that possess high stability and similarity to the native structure. This is accomplished through optimisation of the distances between TM regions and the end-on rotation of each TM helix. The starting point for the genetic algorithm is from the model of general TM region arrangement predicted using the TMRelate program. From these approximate starting coordinates, the TMBuilder program is used to generate the helical backbone 3D coordinates. The amino acid side chains are constructed using the MaxSprout algorithm. The genetic algorithm is designed to represent a TM protein structure by encoding each alpha carbon atom starting position, the starting atom of the initial residue of each helix, and operates by manipulating these starting positions. To evaluate each predicted structure, the SwissPDBViewer software (incorporating the GROMOS force field software) is employed to calculate the free potential energy. For the first time, a GA has been successfully applied to the problem of predicting membrane protein structure. Comparison between newly predicted structures (tests) and the native structure (control) indicate that the developed GA approach represents an efficient and fast method for refinement of predicted TM protein structures. Further enhancement of the performance of the GA allows the TMGA system to generate predictive structures with comparable energetic stability and reasonable structural similarity to the native structure.en
dc.language.isoenen
dc.publisherUniversity of Bedfordshireen
dc.subjectC710 Applied Molecular Biology, Biophysics and Biochemistryen
dc.subjectprotein structuresen
dc.subjectmembrane protein structureen
dc.subjectdrug discoveryen
dc.subjectgenetic algorithmen
dc.titleDevelopment of genetic algorithm for optimisation of predicted membrane protein structuresen
dc.typeThesis or dissertationen
dc.type.qualificationnamePhDen_GB
dc.type.qualificationlevelPhDen
dc.publisher.institutionUniversity of Bedfordshireen
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