Platform>Membrane AIMD>Membrane (GPCR) AIMD platform

Membrane AIMD

From The Mind Come Drugs of the Future

01

Preparing complex and topology

  • 1

    Target protein from X-ray, NMR, or Cryo-EM

  • 2

    Formatting Initial PDB to GROMACS types (gro, itp, top, et al.)

    • $> gmx pdb2gmx -f step1pdbreader.pdb -o complex.gro -ignh -ter -ss -water spc -merge all -missing
02

Orienting Bilayer/Micelle to Protein

  • 1

    Adding POPC bilayer to NTSR1 receptor

  • 2

    Packing the lipids around the receptor (InflateGro)

    • $> gmx editconf -f complex.gro -o complex_align1.gro -box 6.23910 6.17970 9.80000 -princ -rotate 0 -90 0
    • $> perl commonfiles/inflategro.pl system1.gro 4 POPC 14 system1_inflated0.gro 5 area.dat
03

Solvating a Membrane-Receptor

  • 1

    Adding Solvent Water to Top/Bottom of lipid

  • 2

    Adding Neutralizing Counter-ions

  • 3

    Energy minimization for avoiding atomic crash

    • $> gmx solvate -cp system1_newbox.gro -cs spc216.gro -o system1_solv.gro –p topol.top
    • $> python2 commonfiles/removeWaters.py system1_solv.gro system1_solv1.gro
04

Equilibrating & Production

  • 1

    Equilibrating previously prepared receptor (Solute) and water-bilayer (Solvent)

  • 2

    Run production MD for well-equilibrated system at the desired temperature and Pressure

    • $> gmx grompp -f commonfiles/nvt.mdp -c em.gro -r em.gro -p topol.top -n index_ini.ndx -o nvt.tpr
05

Post-Analysis for In-silico Hits

  • 1

    For stability and flexibility of receptor (RMSD/RMSF)

  • 2

    Receptor-Ligand binding affinity (MM/GBSA & BAR)

  • 3

    Density of the Membrane