The open state of human topoisomerase I as probed by molecular dynamics simulation.

ABSTRACT: The open state of human topoisomerase I has been probed by molecular dynamics simulation, starting from the coordinates of the closed structure of the protein complexed with DNA, after elimination of the 22-bp DNA duplex oligonucleotide. A repulsion force between the two lips of the protein has been introduced for a short time to induce destabilization of the local minimum, after which an unperturbed simulation has been carried out for 10 ns. The simulation shows that the protein undergoes a large conformational change due to rearrangements in the orientation of the protein domains, which however move as a coherent unit, fully maintaining their secondary and tertiary structures. Despite movements between the domains as large as 80-90 A, the catalytic pentad remains preassembled, the larges

SUBMITTER: Chillemi G 

PROVIDER: S-EPMC1888835 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature