Project 1: Investigating the role of ligand flexibility in the binding of myristate to I-FABP And Project 2: Studying the effect of the bacterial NDK proteins on haemopoietic stem cells

Liepina, Inara (2014). Project 1: Investigating the role of ligand flexibility in the binding of myristate to I-FABP And Project 2: Studying the effect of the bacterial NDK proteins on haemopoietic stem cells. University of Birmingham. M.Res.

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Abstract

The first project is based on investigating the role of ligand flexibility in the binding of myristate to IFABP. Myristate and palmitate bind the protein I-FABP with affinities orders of magnitude higher than similar sized less flexible ligands. This seems to contradict the medicinal chemistry textbooks where making a ligand less flexible is an accepted method for increasing binding affinity. Here computer simulations were used to investigate myristate flexibility and its free energy of binding to I-FABP, to see what role flexibility has in the recognition of myristate by 1-FABP. The second project is based on studying the effect of the bacterial NDK proteins on haemapoietic stem cells. Leukaemia patients lack immunity; thus bacterial infections worsen leukaemia prognosis. It might be that bacterial invasion can affect leukaemia cells, by rendering the latter more aggressive, or even by stimulating cell proliferation. Bacterial and eukaryotic NDK proteins are highly conserved indicating that they may also be functionally similar. Previously it was shown that additional rNM23-Hl indirectly promotes leukaemia and healthy stem cell survival and proliferation. Here it was investigated if bacterial NDK proteins can show a similar effect.

Type of Work:	Thesis (Masters by Research > M.Res.)
Award Type:	Masters by Research > M.Res.
Licence:
College/Faculty:	Colleges (2008 onwards) > College of Life & Environmental Sciences
School or Department:	School of Biosciences
Funders:	None/not applicable
Subjects:	Q Science > QR Microbiology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
URI:	http://etheses.bham.ac.uk/id/eprint/5308

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