Nanosecond molecular dynamics of HIV protease-inhibitor complexes: Insight into the differential binding potency of diastereoisomers.

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Authors

LEPŠÍK Martin KŘÍŽ Zdeněk HAVLAS Zdeněk

Year of publication 2003
Type Article in Proceedings
Conference Materials in Structure Chemistry, Biology, Physics and Technology
MU Faculty or unit

Faculty of Science

Citation
Web http://www.xray.cz/setkani
Field Physical chemistry and theoretical chemistry
Keywords HIV Protease; molecular dynamics
Description The inhibitory potency of four nanomolar diastereomeric inhibitors of HIV-1 protease [1] was studied by molecular dynamics simulations and MM-GBSA/PBSA analysis. As a starting point we used the crystal structures of protease-inhibitor complexes [2, 3]. Having added hydrogens, we surrounded the complexes with a box of explicit water molecules and added counterions to neutralize the box. Using AMBER 7 program package [4], we minimized, heated and equilibrated the system after which we ran 2-nanosecond-long production dynamics. Periodic boundary conditions were used and long-range electrostatics was treated by particle mesh Ewald (PME) technique. An analysis of the molecular dynamical trajectories was performed and their quality assessed. The protease-inhibitor binding energies were calculated with MM-GBSA/PBSA approach. The effect of the length of the simulation, method to calculate solvation energy, and other factors upon the results was determined.
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