Molecular Dynamics of Protein-Ligand Docking

Modeling, simulations and structural visualizations were performed using MOE 2019 (Chemical Computing Group ULC, Montreal, CA) based on RCSB Protein Data Bank structure 2I66.^{72 (link)} The protein was protonated at T = 310 K, pH 7.0, salt at 200 mM using GB/VI electrostatics. Docking simulations used flexible receptor and flexed the ligand, while docking targeted the active site. For each docking simulation initial placement calculated 50 poses using triangle matching with London dG scoring, the top 5 poses were refined using forcefield Amber10:ETH and Affinity dG scoring (Escore2). The top pose was used then refined using molecular dynamics. Molecular dynamics used the NPA algorithm and the Amber10:ETH forcefield. Solvent was a water droplet with 0.1 M NaCl and used 9518 solvent molecules. Simulation protocol was an equilibrium step for 100 ps at 300 K and a production step for 500 ps at 300 K with a step time of 0.5 ps.