Hi,
calculating the absolute binding energy of a ligand via TI is a bit more
difficult than what is shown in the tutorial. Since the decoupled ligand
would be free to float away from the binding site, you have to add
restraints to the system and account for their free energy effect.
In principle, the following steps apply:
1. add suitable restraints to your complex
2. remove the charge from your restrained ligand
3. decouple your chargeless, restrained ligand from the complex
4. reappear your chargeless, unrestrained ligand in water
5. charge your unrestrained ligand in water
6. apply an analytical correction for the restraints
only steps 3 and 4 would use soft core potentials (ifsc=1). I can't go
over all the details in an email, but look e.g. at reference [125] in the
Amber10 manual, which describes a very similar simulation and the detailed
theory behind it.
All this can be done in Amber10, but the setup may be a bit difficult as
of yet. I am planning to have a tutorial on performing such calculations
with Amber11 up in the near future.
Kind Regards,
Thomas
Dr. Thomas Steinbrecher
BioMaps Institute
Rutgers University
610 Taylor Rd.
Piscataway, NJ 08854
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Thu Jan 14 2010 - 10:00:03 PST
