| Popis: |
DNA dependent DNA polymerases (DNA pols) are key enzymes providing the processes of DNA replication and reparation in living systems. Exceptional importance of DNA pols makes them to be attractive targets for specific low-molecular weight inhibitors, which can be used (and are actually used) as molecular tuning tools in molecular biology investigations, and as antineoplastic and antiviral drugs as well. Detailed comprehension of structural insights of pol–inhibitor interaction would not only give a possibility to design new drugs with highly selective activity with respect to the targeted polymerases, but would essentially extend our understanding of the structural basis of replicative/reparative processes as a whole. Several computational approaches including sophisticated modeling of protein structure, blind and site-oriented docking of inhibitor molecules, molecular dynamics simulation of pol–inhibitor complexes and free energy decomposition analysis are useful tools to improve the quality of structural analysis of pol–inhibitor interactions as well as selectivity of pols’ inhibitors developed de novo. Extended application of these methods is principle tendency in modern rational design, including search and/or design of new inhibitors of DNA polymerases. |
