HIV-1 integrase catalytic core: Molecular dynamics and simulated fluorescence decays

Two molecular dynamics simulations have been carried out on the HIV-1 integ rase catalytic core starting from fully determined crystal structures. Duri ng the first one, performed in the absence of divalent cation (6-ns long), the catalytic core took on two main conformations. The conformational trans ition occurs at approximately 3.4 ns. In contrast, during the second one, i n the presence of Mg2+ (4-ns long), there were no such changes. The molecul ar dynamics simulations were used to compute the fluorescence intensity dec ays emitted by the four tryptophan residues considered as the only chromoph ores. The decay was computed by following, frame by frame, the amount of ch romophores that remained excited at a certain time after light absorption. The simulation took into account the quenching through electron transfer to the peptide bond and the fluorescence resonance energy transfer between th e chromophores. The fit to the experimental intensity decays obtained at 5 degreesC and at 30 degreesC is very good. The fluorescence anisotropy decay s were also simulated. Interestingly, the fit to the experimental anisotrop y decay was excellent at 5 degreesC and rather poor at 30 degreesC. Various hypotheses such as dimerization and abnormal increase of uncorrelated inte rnal motions are discussed.