1. 240 ns of molecular dynamic (MD) simulations.
DYNAMICS OF RILPIVIRINE BINDING WITH WILD TYPE AND K103N MUTATED HIV-1 RT Bilal Nizami, Bahareh Honarparvar Discipline of Pharmaceutical Sciences, School of Health sciences
Introduction
5.6 million HIV infection in SA.
Drug resistance due to mutation (K103N).
Rilpivirine inhibits WT and mutant RT.
Methods
240 ns of molecular dynamic (MD) simulations.
MD - time dependent behavior of a molecular system.
WT and K103N RT, complexed with rilpivirine.
PCA to identify the correlated motion of the RT sub-domains.
Thermodynamics binding free energy by MM(GB)SA method.
Dynamic pharmacophores mapping.

2. DYNAMICS OF RILPIVIRINE BINDING WITH WILD TYPE AND K103N MUTATED HIV-1 RTWT
Fig: Ligand shape inside binding pocket
Fig: Ligand RMSD inside binding pocket
Results
significant role of flexible thumb and finger sub-domains of RT in its biological activity.
rilpivirine is able to adopt different conformations inside binding pocket.
free energy calculations of rilpivirine with mutant HIV-1 RT are in agreement with experimental data.
Fig: sub-domain’s motion in HIV-1 RT

3. DYNAMICS OF RILPIVIRINE BINDING WITH WILD TYPE AND K103N MUTATED HIV-1 RT
Conclusion
Rilpivirine adopts different conformation due to “jiggling” and “wiggling” inside the NNRTI binding pocket of HIV-1 RT, indicating structural flexibility, thereby bypassing the drug resistance.
Dynophore suggest that the better resistance tolerance of rilpivirine comes from binding to LYS 101 in K103N mutated RT, rather than interaction with Asn 103 for the K103N mutant.
Fig: Dynophores of K103N RT
Fig: Dynophores of WT RT
Publication: Bilal Nizami, Dominique Sydow, Gerhard Wolber and Bahareh Honarparvar, Mol. BioSyst., 2016, DOI:  /C6MB00428H