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 molecules of 4-acetylamino-5-hydroxy naphthalene 2-7-disulfonic acid (Y-3) in the catalytic domain (residues 54–199) of avian sarcoma virus integrase (ASV-IN) dimer. Starting model was obtained on the basis of PDB coordinates (PDB code 1A5X) of ASV-IN-Y3 monomer by Lubkowski et al. Proc. Natl Acad. Sci. 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 minimization (EM) and MD simulation were carried out using Sander's module of : Assisted Model building with Energy Refinement: a computer simulation software developed by the University of California, USA, 1997] with all atom force field for Y3 and united atom force field for IN. Analysis of the ligand protein interaction and perturbative changes in the complex is presented in the paper. Salient features related to higher pharmacological activity of Y-3 compared to other analogs from acetyl-amino-naphthalene series are enumerated.