Molecular modeling and molecular dynamics simulations of recombinase Rad51.

The Rad51 ATPase plays central roles in DNA homologous recombination. Yeast Rad51 dimer structure in the active form of the filament was constructed using homology modeling techniques, and all-atom molecular dynamics (MD) simulations were performed using the modeled structure. We found two crucial interaction networks involving ATP: one is among the γ-phosphate of ATP, K(+) ions, H352, and D374; the other is among the adenine ring of ATP, R228, and P379. Multiple MD simulations were performed in which the number of bound K(+) ions was changed. The simulated structures suggested that K(+) ions are indispensable for the stabilization of the active dimer and resemble the arginine and lysine fingers of other P-loop containing ATPases and GTPases. MD simulations also showed that the adenine ring of ATP mediates interactions between adjacent protomers. Furthermore, in MD simulations starting from a structure just after ATP hydrolysis, the opening motion corresponding to dissociation from DNA was observed. These results support the hypothesis that ATP and K(+) ions function as glue between protomers.