The atomistic simulation of potential angiogenic inhibitors.

This thesis concerns the atomistic investigation of the extra-cellular protein angiogenin. The main aims of this project are to propose new potential inhibitors to the angiogenin, and to investigate how they might bind to the protein. Two main families of inhibitors have been investigated; firstly, anthracycline antineoplastic antibiotics of which adriamycin is the parent drug; and secondly, uridine and cytidine nucleotide derivatives. The project has been divided into four research areas; conformational analysis of adriamycin; conformational analysis of nucleotide derivatives; a comparative study of the published crystal structure of angiogenin and a published in-house homology model of the protein; finally a series of docking studies to explore the similarity of the active site of angiogenin to ribonuclease A. Angiogenin has been shown to be 68% similar to ribonuclease A on an atom-by-atom basis, and a new sequence alignment has been produced following the release of the crystal structure of angiogenin