title: Comparison of multiple molecular dynamics trajectories calculated for the drug-resistant HIV-1 integrase T66I/M154I catalytic domain.
abstract: HIV-1 integrase (IN) is an essential enzyme for the viral replication and an interesting target for the design of new pharmaceuticals for multidrug therapy of AIDS. Single and multiple mutations of IN at residues T66, S153, or M154 confer degrees of resistance to several inhibitors that prevent the enzyme from performing its normal strand transfer activity. Four different conformations of IN were chosen from a prior molecular dynamics (MD) simulation on the modeled IN T66I/M154I catalytic core domain as starting points for additional MD studies. The aim of this article is to understand the dynamic features that may play roles in the catalytic activity of the double mutant enzyme in the absence of any inhibitor. Moreover, we want to verify the influence of using different starting points on the MD trajectories and associated dynamical properties. By comparison of the trajectories obtained from these MD simulations we have demonstrated that the starting point does not affect the conformational space explored by this protein and that the time of the simulation is long enough to achieve convergence for this system.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Padova, 35131 Padova, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Brigo
authors.forename: Keun Woo
authors.initials: KW
authors.lastname: Lee
authors.forename: Gabriela
authors.initials: G
authors.lastname: Iurcu Mustata
authors.forename: James M
authors.initials: JM
authors.lastname: Briggs
mesh_terms: D001703:Biophysics / Q000379:methods*; D002244:Carbon / Q000737:chemistry; D020134:Catalytic Domain; D016000:Cluster Analysis; D003198:Computer Simulation; D024882:Drug Resistance, Viral; D019427:HIV Integrase / Q000737:chemistry*; D019428:HIV Integrase Inhibitors / Q000737:chemistry; D019426:Integrases / Q000378:metabolism; D046911:Macromolecular Substances / Q000737:chemistry; D008958:Models, Molecular; D008962:Models, Theoretical; D008968:Molecular Conformation; D009154:Mutation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012984:Software; D013997:Time Factors
chemical_list: D019428:HIV Integrase Inhibitors; D046911:Macromolecular Substances; D002244:Carbon; D019427:HIV Integrase; D019426:Integrases