Computational protocol: Ligand-Based and Structure-Based Investigation for Alzheimer's Disease from Traditional Chinese Medicine

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Protocol publication

[…] Prior to virtual screening, Change Ionization in the Prepare Ligands module (DS 2.5) was applied to adjust ionization states of the downloaded ligands. Downloaded ligands and Tacrolimus were docked to the PPIase domain of FKBP52 under a forcefield of Chemistry at HARvard Molecular Mechanics (CHARMm) using the LigandFit module. Ligands were evaluated based on structural compatibility to the PPIase domain and dock score was selected as the scoring function. [...] Candidates and Tacrolimus were prepared with SwissParam (http://swissparam.ch/) [] prior to MD. MD simulation was conducted with GROMACS 4.0.7 under the forcefield of CHARMm27. Distance of protein to box boundaries was 1.2 nm; solvate TIP3P water model was then added to the system. Complex charges were neutralized with sodium and chloride ions using 0.145 M salt model. Simulation was conducted at 310 K under a pressure of 1 bar. Each complex was minimized with 5,000 steps of Steepest Descent, and the final minimized structure was used as the initial structure for MD simulation. Electrostatic interactions were calculated with Particle-Mesh-Ewald (PME) []. Equilibration protocol was used to restrain and relax protein-ligand position; first-order kinetics was started from 300 K. Minimized system was used to simulate a five-thousand ps configuration production. MD simulation was conducted for 20 ns with time steps of 2 fs under PME. […]

Pipeline specifications

Software tools CHARMM, PHENIX, SwissParam, GROMACS
Applications Drug design, Protein structure analysis
Diseases Alzheimer Disease, Neurodegenerative Diseases
Chemicals Tacrolimus