DNA Dependent DNA Polymerases as Targets for Low-Weight Molecular Inhibitors: State of Art and Prospects of Rational Design

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