2004 IRISH SCIENTIST YEAR BOOK

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University College Dublin
Jens Erik Nielsen
Computers in Biology – no more experiments?
Proteins are large molecules that are produced by cells according to highly specific instructions in the genome. A significant fraction of proteins are capable of speeding up chemical reactions. These proteins are called 'enzymes', and are one of the foundations for life as we know it.


Two forms of a Protein Kinase: Left: unactive conformation, Right: active conformation – computational modelling of the activation process benefits drug design efforts

Enzymes are immensely useful in living organisms, but have also found a wide range of applications in both industrial and household processes. Enzymes are, for example, a common ingredient in washing powder, and are also applied in wineries and bakeries. Furthermore, the majority of pharmaceutical drugs act on enzymes in the human body. The study of enzymes and methods for manipulating enzymes is therefore of significant interest.

At present, time-consuming and expensive experimental studies comprise the overwhelming majority of studies on enzymes, and large amounts of time and money can therefore be saved if computational methods were capable of calculating the characteristics of enzymes. The characteristics of enzymes are best predicted when the 3D-structure of the enzyme is available, and consequently we are developing algorithms for analysing enzyme 3D-structures.

The development of accurate computational algorithms for the study of enzymes must take place in conjunction with experimental work to validate the theoretical predictions. We are concentrating our efforts in three areas: the protein kinase activation process, the pH-dependence of enzyme catalysis, and the importance of thermal motions for enzyme activity. All three projects aim to improve our ability to substitute experiments with theoretical calculations and, to achieve this goal, we carefully evaluate our theoretical predictions by performing wet-lab experiments.

The project concerning the activation process of the protein kinases (PKs) is of particular importance, since the protein kinases are enzymes that are involved in numerous diseases and, most prominently, in a number of cancers. A computational model that describes the PK activation process accurately will allow for significant advances in the development of drugs for treating cell signalling disorders and cancers.

Contact: Dr Jens Erik Nielsen, Department of Biochemistry, University College Dublin, Dublin 4;
Tel: +353 1 716 6724; E-mail: [email protected] ; Web: http://enzyme.ucd.ie