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

Abstract:

:Two molecular dynamics simulations have been carried out on the HIV-1 integrase catalytic core starting from fully determined crystal structures. During the first one, performed in the absence of divalent cation (6-ns long), the catalytic core took on two main conformations. The conformational transition occurs at approximately 3.4 ns. In contrast, during the second one, in the presence of Mg(2+) (4-ns long), there were no such changes. The molecular dynamics simulations were used to compute the fluorescence intensity decays emitted by the four tryptophan residues considered as the only chromophores. The decay was computed by following, frame by frame, the amount of chromophores 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 the chromophores. The fit to the experimental intensity decays obtained at 5 degrees C and at 30 degrees C is very good. The fluorescence anisotropy decays were also simulated. Interestingly, the fit to the experimental anisotropy decay was excellent at 5 degrees C and rather poor at 30 degrees C. Various hypotheses such as dimerization and abnormal increase of uncorrelated internal motions are discussed.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Laboulais C,Deprez E,Leh H,Mouscadet JF,Brochon JC,Le Bret M

doi

10.1016/S0006-3495(01)75715-3

subject

Has Abstract

pub_date

2001-07-01 00:00:00

pages

473-89

issue

1

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(01)75715-3

journal_volume

81

pub_type

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