This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.104.050286v1 88/5/3072    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brigo, A. Articles by Briggs, J. M. Search for Related Content PubMed PubMed Citation Articles by Brigo, A. Articles by Briggs, J. M.

Comparison of Multiple Molecular Dynamics Trajectories Calculated for the Drug-Resistant HIV-1 Integrase T66I/M154I Catalytic Domain

Alessandro Brigo ^*, Keun Woo Lee , Gabriela Iurcu Mustata  and James M. Briggs 

^* Dipartimento di Scienze Farmaceutiche, Università degli Studi di Padova, 35131 Padova, Italy; and Department of Biology and Biochemistry, University of Houston, Houston, Texas 77024-5001

Correspondence: Address reprint requests to James M. Briggs, Dept. of Biology and Biochemistry, University of Houston, Houston, TX 77204-5001. Tel.: 713-743-8366; Fax: 713-743-8351; E-mail: jbriggs{at}uh.edu.

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.

This article has been cited by other articles:

				C. N. Alves, S. Marti, R. Castillo, J. Andres, V. Moliner, I. Tunon, and E. Silla A Quantum Mechanic/Molecular Mechanic Study of the Wild-Type and N155S Mutant HIV-1 Integrase Complexed with Diketo Acid Biophys. J., April 1, 2008; 94(7): 2443 - 2451. [Abstract] [Full Text] [PDF]

				N. Nunthaboot, S. Pianwanit, V. Parasuk, J. O. Ebalunode, J. M. Briggs, and S. Kokpol Hybrid Quantum Mechanical/Molecular Mechanical Molecular Dynamics Simulations of HIV-1 Integrase/Inhibitor Complexes Biophys. J., November 15, 2007; 93(10): 3613 - 3626. [Abstract] [Full Text] [PDF]