From: Jeffrey Potoff (jpotoff_at_chem1.eng.wayne.edu)
Date: Thu Jul 07 2011 - 17:16:02 CDT
Why not use the adaptive force bias method?
http://www.edam.uhp-nancy.fr/ABF/
http://www.ks.uiuc.edu/Training/Tutorials/namd/ABF/tutorial-abf.pdf
On 7/7/2011 6:08 PM, Gianluca Interlandi wrote:
> Francesco,
>
> 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.
>
> Tutto chiaro?
>
> Gianluca
>
> 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.
>> chiendarret
>>
>> 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:
>>> http://glycam.ccrc.uga.edu/ccrc/GlycamLITE/Protein/uploadIndex.jsp?option=ff99
>>>
>>> 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
>>> guide.
>>> 4. Run the simulation.
>>> 5. Calculate the free energy of binding following corresponding
>>> steps in the
>>> Amber tutorial:
>>> http://ambermd.org/tutorials/advanced/tutorial3/
>>> Dong
>>>
>>> ________________________________
>>> 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
> http://artemide.bioeng.washington.edu/
>
> Postdoc at the Department of Bioengineering
> at the University of Washington, Seattle WA U.S.A.
> -----------------------------------------------------
-- ====================================================================== Jeffrey J. Potoff jpotoff_at_chem1.eng.wayne.edu Associate Professor Wayne State University Department of Chemical Engineering and Materials Science 5050 Anthony Wayne Dr Phone:(313)577-9357 Detroit, MI 48202 Fax: (313)578-5815 http://potoff1.eng.wayne.edu ======================================================================
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