Date: 17 Apr 2002 From: jyrki@diku.dk Subject: Protein-Protein interaction Oral defence of M.Sc. thesis: Protein-Protein interaction; Heuristic search in databases of 3d protein structures Defender: Hans-Henrik Stærfeldt Censor: Anna Ingolfsdottir, Aalborg University Supervisor: Jyrki Katajainen Time: Monday, 22 April 2002. 13.15–15.00 Place: N037 at DIKU The defence will be held in Danish. Abstract: In protein research and drug development and, when working with new proteins, it is often important to determine how and with which other proteins interaction occurs. Similarly it is of interest to know how these complexes are arranged in 3 dimensions. In this work the goal has been to implement a heuristic search technique which is able to search against a library of 3d protein structures given a query protein's 3d structure. In part the aim has been to implement a set of energy measures to be used when seeking out promising candidates to which the query protein is likely to bind, as well as to determine a configuration of the resulting compound. This is done using a shape complementarity measure, a simple electrostatic interaction model based on partial charges of the protein atoms, and a desolvent measure. The search uses a technique of sampling the energy fields and density of the proteins in a 3d grid allowing for fast ranking of translational configurations to be reached by Fourier correlation theory. To speed up the search the rotational space is clustered and a branch-and-bound algorithm is applied for the search. The method takes into account flexible amino acids by constructing an energy measure which is a bound for the average interaction energy between all possible configurations of the amino acids. However, backbone flexibility is not considered explicitly. The implementation of the method was not finished at the time this thesis was due for evaluation. Therefore, the thesis describes what methods have been used when solving some of the partial problems, as well as which design features are planned for the full implementation. PE-lab's homepage: http://www.diku.dk/~jyrki/PE-lab/