Molecular dynamics studies on the interaction of 4-acetylamino-5-hydroxynapthalene-2,7-disulfonic acid with catalytic domain of avian sarcoma virus integrase dimer

We report here 500 ps molecular dynamics (MD) simulation results on two mol ecules of 4-acetylamino-5-hydroxy naphthalene 2-7-disulfonic acid (Y-3) in the catalytic domain (residues 54-199) of avian sarcoma virus integrase (AS V-IN) dimer. Starting model was obtained on the basis of PDB coordinates (P DB code 1A5X) of ASV-IN-Y3 monomer by Lubkowski et al. [Proc. Natl Acad. Sc i. USA, 95 (1998) 4831-4836]. Two molecules of Y3 were docked in the active cavity of the dimer using IMF [Phys. Edu., 5 (1988) 169-176]. Energy minim ization (EM) and MD simulation were carried out using Sander's module of AM BER 5.0 [AMBER 5.0: Assisted Model building with Energy Refinement: a compu ter simulation software developed by the University of California, USA, 199 7] with all atom force field for Y3 and united atom force field for IN. Ana lysis of the ligand protein interaction and perturbative changes in the com plex is presented in the paper. Salient features related to higher pharmaco logical activity of Y-3 compared to other analogs from acetyl-amino-naphtha lene series are enumerated. (C) 2001 Elsevier Science B.V. All rights reser ved.