Research:GK FEP BAR

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Simulation process and the parameters

The execuable for GK/Bar simulaton is located at: /users/jzhen/tinker5.1-gk-param/source4/

With RESPA multi-step implement (from Tinker6): /users/jzhen/tinker5.1-gk-param/source4-respa/

Relative binding free energy calculation: two states

bound state: protein-ligand in GK solvent

free state: ligand only in GK solvent

In each state, we scale ele first, and then vdW. A example of prameter and key file can be seen at: /users/jzhen/OSRW_GK/GK-bar/lig-pro/lig2-pro/. The ele is scaled from 1.0 to 0 by ele6 --> ele5 -->....ele2 --> ele1 --> vdw6, vdW is scaled from 1.0 to 0 (the well depthe psilon is scaled to 0.0 and the radious is scaled to 0.0001). For each windows, the simulation time is 150ps, timestep is 1.5fs with rattle and 3fs with respa/rattle


Solvation energy comparison

Ligand Published Label PB (published result)

PB-polar

(published)

GK (min structure) PB (min structure) PB (gas-min struct, tinker10-08) PB (gas-min struct, tinker10-08, polar) GK-FEP
Lig 1 A -54.2 -56.8 -61.0707 -53.4881 -54.9396 -56.0900 -60.7210
Lig 2 B -55.6 -58.1 -63.0336 -54.8510 -57.2422 -57.2155 -62.9246
Lig 3 C -58.3 -60.9 -66.6569 -58.7613 -60.1055 -59.9958 -66.5370
Lig 6 D -53.4 -56.2 -59.1056 -53.1730 -54.3039 -55.2043 -58.6448
Lig 4 E -57.6 -60.1 -55.5956 -56.4508 -57.9430 -59.6392 -55.4094
Lig Yue -- -62.5264 -57.8351 -58.6675 -59.0935 -60.4647
  • PB (published) vs GK

Directories

  • /home/wuch/work/research/trypsin-ligand
    • lig1,lig2,lig3,lig4,lig6,lig_yue

Questions

  • Why are some torsion parameters different between the two?
    • /home/oscar/trypsin/lig2/lig-pro/vdw1/vdw1.prm
    • /home/oscar/trypsin/lig2/lig-pro/amoeba.prm