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The principles of soluble protein structure and ligand docking are applied to structure analysis of membrane bound protein receptors and receptor ligand complexes.
Masters/PHD
Approximately 50-60% of marketed drugs target membrane bound receptors such as G-protein coupled receptors, ion channels and transporters. G-protein coupled receptors, containing a seven transmembrane helix topology, are one of the largest families of the human genome, and hence represent an important architecture for the action of drugs. In the last 10 years protein structure determination and assessments of the principles of protein structures has provided computational methods with success in predicting protein structures from the amino acid sequence alone- where no structural analogue is identifiable from sequence similarity. Though they represent extremely difficult experiments, there are now reports of high resolution membrane protein crystal structures, so the field is comparable to the first few years of soluble protein structure determination. As yet, no methods have been determined to be applicable to highthroughput and so the future may be assisted by computational analysis. There are approximately 50 high resolution structures of membrane protein, though they are dominated by proteins from bacterial membranes. In November 2007 the first G-protein coupled receptor drug target structure, human b2-adrenergic receptor, became available. We are developing knowledge-based (bioinformatics) methods for analysing and understanding the structures of integral membrane proteins, and have already showin the value of the judicious application of principles from soluble protein structure. In some ways the principles are simplified by the constraints of a membrane. A number of other principles of membrane protein structures have just emerged and need to be incorporated into our methods. Our bioinformatics interests range from refinements of the analysis of evolutionary pressure to provide alternative protein topologies to computational docking. Our interest in molecular biology and crystallography and their application to structure-based drug design for targets of Schizophrenia, inflammation and cancer give us insights into the requirements necessary to progress in an important area of structural biology.
Techniques used will be bioinformatics, computational biology, computational docking, X-ray crystallography, molecular modeling, statistical potentials, molecular biology, aspects are suitable as Honours projects
The opportunity ID for this research opportunity is 599