Dear Dr. Steinbrecher,
>
>so the end state system prmtop does not contain the ligand. Since you run
>the calculation using groupsander on both prmtops, your ligand will still
>be 'there' at lambda=1, but it will not interact with anything else (but
>maintains its internal potentials).
I am still wondering this issue. As you said, the internal potential of ligand is still remains. But as in State 0 (pro+lig), the energy is: V0=V_pro_internal+V_lig_internal+V_pro_lig, in state 1(pro), only V1=V_pro_internal remains. So the energy difference at lambda=1 equals V_pro_lig+V_lig. How do we include the ligand internal potential in ?
Best wishes,
Bing
------------------
Bing Xiong
2012-01-04
steinbrt
steinbrt.rci.rutgers.edu
>Hi,
>
>> As usually in double decoupling calculation, in V1 state, the ligand still
>> remains, but just not interacted with protein( it is in gas state and
>> usually contraint in origin position). So I still need the ligand in top
>> and crd file. Dr. Donald Hamelberg suggested me to make a frcmod file and
>> modify the vdw parameter to 0.0, but this will also did not calculate the
>> ligand intramolecular interaction. I am wondering is there other way for
>> just turn off the vdw interaction?
>> Thanks !
>
>what Prof. Case said is nevertheless correct. Amber's softcore TI
>implementation requires a setup e.g. like this:
>
>pmrtop V0: Protein+Ligand+Solvent
>prmtop V1: Protein+Solvent
>
>so the end state system prmtop does not contain the ligand. Since you run
>the calculation using groupsander on both prmtops, your ligand will still
>be 'there' at lambda=1, but it will not interact with anything else (but
>maintains its internal potentials).
>
>The alternative way of using 'dummy' atoms (with zero vdW parameters) will
>also work in principle, but is discouraged due to potential severe
>simulation instabilities (all described in more detail in the two Amber
>softcore papers).
>
>So what you want to do is certainly possible in Amber. Check out the
>recommended tutorial. It can be adapted for absolute binding free
>energies, but setting the restraints (in the V1 side of the system)
>requires some planning, since they will be linearly scaled. The manual has
>more on this, see the dvdl_norest option.
>
>Kind Regards,
>
>Thomas
>
>Dr. Thomas Steinbrecher
>formerly at the
>BioMaps Institute
>Rutgers University
>610 Taylor Rd.
>Piscataway, NJ 08854
>
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Received on Tue Jan 03 2012 - 16:30:03 PST
