The Centre for Computational Science


Src Homology 2 domains (SH2)


H2 domains are common protein subunits that can be found in many different tyrosine-kinase mediated signal transduction pathways. They bind and recognise specific peptide sequences containing phoshorylated tyrosines (see figure). Understanding this interaction, it is hoped, will lead to the development of a novel class of drugs that are able to control specific signal transduction pathways and consequently treat a wide range of ailments, from cancer to immunological disorders.

We are studying the binding of different peptide sequences to an SH2 domain using thermodynamic integration. This technique often requires large quantities of computational resource and can take weeks to months to get a result. Through the RealityGrid project, we have developed a grid-based method to accelerate the calculation of differences in binding free energies using thermodynamic integration. This not only speeds up individual calculations, but also makes the process easier from the perspective of the user. For more information please see the conference proceedings paper below.


Fowler,P.W., Coveney,P.V., Jha,S. & Wan,S.