Investigation of drug-enzyme complex using computer-aided drug design approach

1. MD Simulations: Dynamics of flap and Conformational Changes

2. Tip-Tip distance analysis

3. Principal component analysis (PCA) and
Normal Mode Analyses
To qualitatively understand the effect of inhibitor’s binding on
the predominant conformational motion of each residue
Dynamic cross-correlation matrix analysis
The induced internal dynamics of flap on inhibitor’s
binding

4. MD Simulations: Enzyme-Ligand Binding

5.  Identification of 3D-pharmacophore hypotheses
 Screening of compounds library
 Docking-based virtual screening
 ADMET properties assessment
 MD simulations
 Post-dynamics MD: RMSD, RMSF, Rg, SASA HB analysis, PCA and NMA
 Binding Free energies and residual decomposition energies

6. Binding Free Energies analysis