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Contenuto archiviato il 2024-05-29

Towards excellence in computational structural biology and biomaterials

Final Report Summary - COSBIOM (Towards excellence in computational structural biology and biomaterials)

The main objectives of the project COSBIOM were:
(1) to enhance PRC's excellence in the fields of computational structural biology and biomaterials by networking with European research centres through exchange of researchers (visiting scientists, postdoctoral fellows);
(2) to increase PRC's research capacity by upgrading existing computational and experimental resources and by hiring postdoctoral fellows and graduate students;
(3) to ensure the continuity of PRC's overall capacity within the scope of this support action by joint research activities and preparing new project proposals with collaborators in Europe; and
(4) to disseminate all research results through scientific meetings, publications in peer-reviewed journals, and continuous posting of activities and results at website, and by providing novel computational methodologies to the scientific world via the grid infrastructure to be implemented on local computer network.

Proteins are highly flexible molecules. It is common to classify protein motions into shear and hinge motion. Shear motions are very limited and involve large number of residues. On the other hand, hinge motions are similar to rotations around an articulated joint and therefore can be very large. Hinge motion is characterised by large changes in main-chain torsional angles occurring at a localised region, which is called a hinge. Hinge motions usually involve a small number of residues, since even one bond can provide the required rotational freedom.

This kind of protein motion is free of packing constraints. When a chain exhibits hinge motion at the region connecting two structural domains, each domain behaves as a rigid body and packing interactions can appear/disappear between the interfaces of those rigid bodies. Hinge motions usually occur upon binding to another molecule, or upon activation/deactivation of the protein.

Therefore, hinge regions are the mechanistically informative regions of the structure and are of great importance in mediating cooperative motions that have functional importance. Hinge motions usually occur upon binding to another molecule, or upon activation / deactivation of the protein. Therefore, hinge regions are the mechanistically informative regions of the structure and are of great importance in mediating cooperative motions that have functional importance. Hingeprot is a web server for predicting rigid protein parts and the flexible hinge regions connecting them in the native topology of protein chains by employing Elastic network (EN) models. Hingeprot makes use of both 'Gaussian network model' (GNM) and 'Anisotropic network models' (ANM).

Hingeprot is expected to be useful in a range of potential applications, especially in prediction protein-protein association, flexible docking and in refinement of the structure of the modelled complexes. Hingeprot predictions are also helpful in fitting flexible hinge-bent protein structures into EM density maps and refining the EM structures. In addition, hinge regions can help in understanding functional mechanisms of macromolecular structures and assemblies.

Given an input protein chain, Hingeprot identifies the rigid parts and the hinges connecting them, and the direction of the fluctuation of each residue in the slowest two modes. PRC has developed the algorithm and the server in collaboration with the Tel-Aviv university structural bioinformatics group, Israel. There are continuous efforts for the development of the server. Hingeprot has now been extensively tested and the paper that describes the theoretical background and its use is just published. The updates in this reporting period are: improvement of server performance by achieving submitted structures for future usage and updating the visualisation programs to prevent unexpected failures during runs; design of the server more user friendly by changing page layout and allowing the user to change some parameters.

The share of the computational, software and data resources with our collaborators and other external users is achieved by a hybrid computational and data grid infrastructure called COSBIOM that has been installed as of February 2008. Existing computational applications are now grid-enabled, as well as our newly acquired computational servers and data are available as resources on our grid. The COSBIOM grid not only enables our resources to be shared, but also enables us to network and integrate more easily with other Biology grids in Europe.

The web-based COSBIOM project information system was set up during the first year of the project. The intention behind the system is to ease the information sharing between both COSBIOM project members and the interested audience. For this purpose, a content management system and some other third party components have been installed on a web server. The COSBIOM project information system is available at

The system provides the following properties:
- creation, management, distribution, publishing, and discovery of information for the COSBIOM project;
- publishing news related to the COSBIOM project and announcements of the upcoming events;
- sharing documents and publications through a file repository;
- sharing internal information between COSBIOM project members;
- announcing and getting applications for open post doctoral positions;
- syndication.

The foreseen benefits of the project are immediate increase:
(1) in the competency level in developing new computational methodologies in the fields of structural biology and bioinformatics in collaboration with experimental and computational groups in Europe for the solution of important health-related problems; (2) in collaborations related to the design of stereo-selective synthesis of drugs, and design / synthesis of novel multifunctional polymers with applications in dentistry and nanotechnology; and
(3) in computational, experimental and human resources, which will strengthen PRC's research infrastructure and its potential for future participation in the European research platform.

The current project is relevant to several thematic priorities of the sixth framework programme, in particular advanced genomics and its applications for health, bioinformatics, basic biological processes, knowledge-based multifunctional materials, and biomaterials. Through the COSBIOM project and potential participation in the Seventh Framework Programme (FP7), PRC will contribute to both European research and the research and technological development in Turkey.