Role of flexibility and long range communication on the function of human topoisomerase I.

Eukaryotic topoisomerase I is an essential enzyme that regulates the changes in DNA topology, relaxing the superhelical tension associated with DNA replication, transcription and recombination. Human topoisomerase I is of significant medical interest being the only target of the antitumor drug camptothecin. The enzyme undergoes large conformational changes during its catalytic cycle and the knowedge of the degree of flexibility of the different regions provides an useful guide to the understanding of such movements. Molecular dynamics simulation is a well consolidated method for the investigation of structural and dynamic properties of proteins and nucleic acids and has been successfully applied to study the dynamical properties of the DNA-human topoisomerase complex. This review highlights some structural and dynamic properties of topoisomerase, obtained by MD simulations, that permits to explain the importance of flexibility in the modulation of the functional properties of the enzyme and in the transmission of communication between domains located far away one from each other.