Nanosecond molecular dynamics of HIV protease-inhibitor complexes: Insight into the differential binding potency of diastereoisomers.
| Authors | |
|---|---|
| Year of publication | 2003 |
| Type | Article in Proceedings |
| Conference | Materials in Structure Chemistry, Biology, Physics and Technology |
| MU Faculty or unit | |
| 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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