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/