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Oligonucleotides with Heavy Atoms and DNA-Binding Proteins Structural Analysis

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Synthesis of Oligonucleotides wiyh Heavy Atoms and Development of Structural Analysis of DNA-binding Proteins

Tech Area / Field

  • BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
  • BIO-INF/Bioinformatics/Biotechnology

Status
3 Approved without Funding

Registration date
06.07.1997

Leading Institute
Kurchatov Research Center / Institute of Informational Technologies, Russia, Moscow

Supporting institutes

  • Institute of Molecular Genetics, Russia, Moscow

Project summary

In this project we consider to use the experience and knowledge of the group of scientists, who have participated earlier in works on nuclear and chemical security, in fundamental molecular-biological investigations, particularly in the functional and structural investigations of the DNA-binding proteins.

DNA-binding proteins are key-structures for the control of such important cell processes as transcription and proliferation. The processes of cell malignant transformation and of the genome stability control are also influenced by DNA-binding proteins functions. The elaboration of efficient methods of DNA-binding proteins structure analysis (including synthesis of metal-containing DNA-protein complexes for X-ray structural analysis and computer modeling of such molecular structures) should enable us with our partners from Germany and England to decode the structures of several DNA-binding proteins and to explain the principles of their structural organizing. This result could be a breakthrough in resolving the fundamental problem of DNA-protein recognition and could give practical recipes for medical and gen-ingeneering treatment of diseases (such as cancer or other system disordering) caused by the defects of DNA-bindig proteins.

The following researches are proposed in order to achieve the above mentioned results:


1. The elaboration of methods of selective insertion of heavy metal atoms into the oligonucleotide sequences for obtaining DNA-protein complex isomorphic derivatives for X-ray structure analysis;
2. The elaboration of efficient computing methods for 3-d protein structure modeling, using the data on the homology of the initial structures with the known 3-d protein structures from PDB data bank;
3. The determination of DNA-binding protein 3-d structures for proteins with known aminoacids sequences, being homologous to the proteins from PDB bank;
4. The development of the mathematical method and the elaboration of special device for 3-d stereosynthesis with the account of the observer location, the application of this method to protein molecular modeling and to the interpretation of the X-ray data for DNA-binding proteins;
5. Preparing the hypertext data base, integrating the data by DNA-binding proteins properties and functions, their initial and 3-d structures being stored in international data banks (SWISSPROT, EMBL, PDB).


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