From: Gianluca Interlandi (gianluca_at_u.washington.edu)
Date: Thu Jul 07 2011 - 17:08:55 CDT
Just a hint. Don't take my word that this works. I thought that free
energy makes sense to calculate only when you compare it to a reference
point, e.g., you have a mutation and you compare to the wild-type. So, in
this way you have a DeltaG. DeltaG can be written as:
DeltaG = DeltaU - T*DeltaS
DeltaU is the internal energy which can be calculated with namdenergy as
the interaction energy between the ligand and the protein. You want to
include bulk in the calculation (although you might still want to
calculate it for both, with and without bulk).
The hard part, as usual, is estimating DeltaS. Schlitter had come up with
a method to estimate the vibrational entropy from the covariance, which
was then refined by van Gunsteren and even implemented into CHARMM (see
corman.doc and grep "Schlitter"). That might give you an estimate for
DeltaS. However, you need to make sure that your simulations have
converged and you have sampled enough.
On Thu, 7 Jul 2011, Francesco Pietra wrote:
> First, I have the systems equilibrated with charmm ff and it would be
> too much work to change to amber ff. Second, the systems have lipids
> and amber ffs are not so good for lipids. Third, the system is based
> on a multimer protein and amber renumbers continuously all atoms,
> unlike charmm that preserves subunits. Examining interactions with
> continuous numbering will be headache. But it was kind from you to
> give details. I wish you success with the method.
> On Thu, Jul 7, 2011 at 5:50 PM, Dong Luo <us917_at_yahoo.com> wrote:
>> AmberTools has utilities to calculate free energy of binding from a single
>> MD trajectories that simulated with Amber force field. NAMD supports Amber
>> force field.
>> I recently did a test with this. It works though I am not sure of the
>> quality of the results because it's the first time for me to calculate the
>> binding free energy.
>> Briefly the steps are:
>> 1. Convert pdb file to Amber friendly format according to AmberTools'
>> manual. The online tool:
>> can help with it.
>> 2. Using AmberTools' tleap to create parameter and coordinates input files
>> for MD. Again check with the manual.
>> 3. Edit NAMD configuration file to use the Amber force field. Check NAMD's
>> 4. Run the simulation.
>> 5. Calculate the free energy of binding following corresponding steps in the
>> Amber tutorial:
>> From: Francesco Pietra <chiendarret_at_gmail.com>
>> To: NAMD <namd-l_at_ks.uiuc.edu>
>> Sent: Thursday, July 7, 2011 5:52 AM
>> Subject: namd-l: free energy of binding
>> How could free energy of binding of a small-molecule ligand to a
>> protein receptor be calculated from namd md trajectories?
>> Is there a validated specific procedure for namd, or should a
>> literature method be imitated? For example Åqvist's method:
>> Åqvist, J., Medina, C., and Samuelsson, J. E. (1994) A new
>> method for predicting binding a?nity in computer-aided drug design.
>> Protein Eng. 7, 385?391.
>> thanks for sharing experience on this hot topic
>> francesco pietra
Gianluca Interlandi, PhD gianluca_at_u.washington.edu
+1 (206) 685 4435
Postdoc at the Department of Bioengineering
at the University of Washington, Seattle WA U.S.A.
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