Date: 10 Sep 2009 From: jyrki@diku.dk Subject: Thesis defence on protein interactions Oral defence of M.Sc. thesis: Searching for similar binding sites Defender: Anders Thøgersen Censor: Christian Storm Pedersen Supervisor: Jyrki Katajainen Time: 17 September 2009 at 11.00–12.00 Place: N026 The defence will be held in Danish. Abstract In protein research it is often important to determine with which other proteins an interaction may occur. This can help in definition of biological role of the protein, such as inhibition or enhancement of particular functions. The criterion that makes an interaction possible is that the two proteins contain binding sites that structurally and chemically allow the interaction to take place. In this work a method is developed to allow the deduction of possible new protein interactions by looking at the set of protein interactions that are already known. A framework has been created for experimenting with superimposition of protein binding sites. The central methods employed are Particle Swarm Optimization and Iterative Closest Point. Because the same protein binding site may have variations across protein families, the removal of outliers, i.e. atoms that should be discarded to achieve a good superimposition of the binding site core, has been a central theme of this work. The developed methodology is calibrated on representative data and the quality of superimpositions made is compared with MultiBind, an existing program for solving this problem that uses a fundamentally different approach. Good superimpositions are achieved with geometrically similar structures, but biologically significant results are obtained less frequently. However, some experiments indicate that there is room for significantly improving performance on biologically significant results. The thesis is available online: http://www.diku.dk/~jyrki/PE-lab/Anders/ PE-lab's home page: http://www.diku.dk/~jyrki/PE-lab/