Servizio Comunitario di Informazione in materia di Ricerca e Sviluppo - CORDIS

Final Activity Report Summary - PROTCOMPLEXMODEL (Molecular modelling-based charaterization of protein complexes involved in DNA repair)

The focus of this project was the development of computational tools to study three-dimensional structures of protein complexes and application of these tools to advance the understanding of DNA repair processes. Stable or transient protein complexes underlie most cellular processes, therefore the knowledge of how proteins interact as three-dimensional structures is the key for understanding of these processes. On the other hand, determination of structures for protein complexes by experimental methods is slow, expensive and often unfeasible. Therefore the development of computational methods is critically important to tackle this problem. In this project we used comparative or homology modelling approach, which is based on the observation that related proteins and to a large degree protein complexes share similar three-dimensional structures.

Among the main objectives of the project was to improve the ability to produce accurate models even for distantly related proteins/protein complexes. We have made a number of improvements to our earlier comparative modelling approach and tested it during the world-wide contest of protein structure prediction methods. This contest, known as CASP (Critical Assessment of Structure Prediction), is run in a 'blind' mode, i.e. the answers are not known in advance. Because of that CASP provides a possibility to test and compare different modelling methods at the same time frame on the same set of proteins. The independent assessment has ranked our results obtained with the improved modelling approach as being among the best. In the course of the project we also developed a database of protein complexes, where proteins are represented as three-dimensional shapes at the atomic resolution. We believe that the database can be a useful resource both for modelling new protein complexes and for studying general properties of known protein interactions. In addition we have applied modelling methods to study several pathways of DNA repair. In joint studies with experimental biologists, these models have revealed important new findings regarding molecular mechanisms in DNA repair.

Reported by

Graiciuno 8
See on map