Re: free energy of binding

From: Gianluca Interlandi (gianluca_at_u.washington.edu)
Date: Thu Jul 07 2011 - 17:29:18 CDT

Of course you can, but I think that Francesco is asking about an analysis
method of his already performed trajectories.

Gianluca

On Thu, 7 Jul 2011, Jeffrey Potoff wrote:

> 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
> ======================================================================
>
>

-----------------------------------------------------
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.
-----------------------------------------------------

This archive was generated by hypermail 2.1.6 : Wed Feb 29 2012 - 05:24:11 CST