Re: free energy of binding

From: Richard Wood (
Date: Thu Jul 07 2011 - 18:56:48 CDT

Of course, one could use the method of Tokarski and Hopfinger which is a general method and works regardless of the FF used. Richard ________________________________ From: Jeff Wereszczynski <> To: NAMD <> Sent: Thu, July 7, 2011 6:27:55 PM Subject: Re: namd-l: free energy of binding Francesco, You've actually asked what is a difficult question that contains many complexities. I'd suggest checking out a review on the subject before diving in, for example Gilson and Zhou had a very nice one, here is the reference: Annu. Rev. Biophys. Biomol. Struct 2007. 36:21–4 Best, Jeff On Thu, Jul 7, 2011 at 4:29 PM, Gianluca Interlandi <> wrote: 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? >> >> >> >> >>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 <> 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 >>>>>guide. >>>>>4. Run the simulation. >>>>>5. Calculate the free energy of binding following corresponding steps in the >>>>>Amber tutorial: >>>>> >>>>>Dong >>>>> >>>>>________________________________ >>>>>From: Francesco Pietra <> >>>>>To: NAMD <> >>>>>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 >> +1 (206) 685 4435 >> >> >>Postdoc at the Department of Bioengineering >>at the University of Washington, Seattle WA U.S.A. >>----------------------------------------------------- >> > >-- >====================================================================== >Jeffrey J. Potoff >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 > >====================================================================== > > > ----------------------------------------------------- Gianluca Interlandi, PhD +1 (206) 685 4435 Postdoc at the Department of Bioengineering at the University of Washington, Seattle WA U.S.A. ----------------------------------------------------- -- Jeff Wereszczynski NIH Postdoctoral Fellow University of California, San Diego

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