**From:** Sadegh Faramarzi Ganjabad (*safaramarziganjabad_at_mix.wvu.edu*)

**Date:** Fri Oct 06 2017 - 14:19:56 CDT

**Next message:**Brian Radak: "Re: convergence criterion of free energy perturbation (FEP) simulations for pKa calculation"**Previous message:**Brian Radak: "Re: convergence criterion of free energy perturbation (FEP) simulations for pKa calculation"**In reply to:**Brian Radak: "Re: convergence criterion of free energy perturbation (FEP) simulations for pKa calculation"**Next in thread:**Brian Radak: "Re: convergence criterion of free energy perturbation (FEP) simulations for pKa calculation"**Reply:**Brian Radak: "Re: convergence criterion of free energy perturbation (FEP) simulations for pKa calculation"**Messages sorted by:**[ date ] [ thread ] [ subject ] [ author ] [ attachment ]

Brian,

I just simply want to calculate pKa of a GLU residue in a membrane protein

interior from DeltaG. I already have extra bonds on. Also, alchVdwLambdaEnd

is already 1.0, with alchBondDecouple on.

Apparently, ParseFEP does not split the FEP output file.

Thanks,

Sadegh

On Fri, Oct 6, 2017 at 3:11 PM, Brian Radak <bradak_at_anl.gov> wrote:

*> Hm - that might be a bug in the output; I'll have to check.
*

*>
*

*> By default the bonded terms are not scaled, since this is not usually what
*

*> people want to do.
*

*>
*

*> If you want to compute a relative free energy, then in your case you
*

*> should set:
*

*> alchBondLambdaEnd 1.0
*

*> alchBondDecouple on
*

*>
*

*> and then add extraBonds.
*

*>
*

*> I have no idea if that is what you want to compute -- why are you running
*

*> this simulation?
*

*>
*

*> parseFEP should very happily take different amounts of input, although I'm
*

*> not sure that it permits subsampling of the loaded files. It also assumes
*

*> that the number of samples from all lambdas are equivalent.
*

*>
*

*> You would have to load some files, run the BAR calculation, then load
*

*> additional files and run the BAR calculation again.
*

*>
*

*> HTH,
*

*> Brian
*

*>
*

*>
*

*>
*

*> On 10/06/2017 03:04 PM, Sadegh Faramarzi Ganjabad wrote:
*

*>
*

*> Brian,
*

*>
*

*> Thanks replying.
*

*> 1) Regarding bonded terms, I thought they are already included; in the log
*

*> files I have these lines
*

*>
*

*> FEP CURRENT LAMBDA VALUE 0
*

*> Info: FEP ELEC. ACTIVE FOR ANNIHILATED PARTICLES BETWEEN LAMBDA = 0 AND
*

*> LAMBDA = 0.5
*

*> Info: FEP ELEC. ACTIVE FOR EXNIHILATED PARTICLES BETWEEN LAMBDA = 0.5 AND
*

*> LAMBDA = 1
*

*> Info: FEP VDW ACTIVE FOR ANNIHILATED PARTICLES BETWEEN LAMBDA = 0 AND
*

*> LAMBDA = 1
*

*> Info: FEP VDW ACTIVE FOR EXNIHILATED PARTICLES BETWEEN LAMBDA = 0 AND
*

*> LAMBDA = 1
*

*> Info: FEP BOND ACTIVE FOR ANNIHILATED PARTICLES BETWEEN LAMBDA = 0 AND
*

*> LAMBDA = 1
*

*> Info: FEP BOND ACTIVE FOR EXNIHILATED PARTICLES BETWEEN LAMBDA = 0 AND
*

*> LAMBDA = 1
*

*>
*

*> ****
*

*> FEPTITLE: TS BOND2 ELECT2 VDW2
*

*> ****
*

*> FEP: 0 22006.7270 -93162.0780 2413.1778
*

*> *****
*

*>
*

*> If not, how could I include them?
*

*>
*

*> 2) How necessary it is to compute a difference in relative solvation free
*

*> energies?
*

*>
*

*> 3) Is there a way I could do study long time behavior of the BAR estimate
*

*> of the cumulative data with the ParseFEP plugin? I assume I should split
*

*> the entire simulation to smaller fractions?
*

*>
*

*> Best,
*

*> Sadegh
*

*>
*

*> On Thu, Oct 5, 2017 at 4:30 PM, Brian Radak <bradak_at_anl.gov> wrote:
*

*>
*

*>> Does your transformation also include bonded terms? You will not compute
*

*>> a relative ionization free energy if you do not include those terms,
*

*>> although you can, in principle, compute a difference in relative solvation
*

*>> free energies by doing the corresponding calculation in the gas phase. I
*

*>> don't know your reasons for running your simulation, but I feel that I
*

*>> should point this out -- there are new keywords as of NAMD 2.11 for doing
*

*>> this (see the user guide).
*

*>>
*

*>> Agreement between the forward and backward FEP calculations is only a
*

*>> necessary condition for FEP convergence -- it is neither a sufficient
*

*>> condition for convergence nor a meaningful condition for other estimators,
*

*>> such as BAR.
*

*>>
*

*>> Another necessary, but still not sufficient, condition for convergence
*

*>> might be found in the long time behavior of the BAR estimate of the
*

*>> cumulative data (i.e. use the first 10 ns, then the first 20 ns, etc. and
*

*>> see if the answer changes as the simulation gets longer).
*

*>>
*

*>> The forward and backward construction loses all meaning when analyzing
*

*>> with thermodynamic integration, for the same reason as it does for BAR.
*

*>>
*

*>> HTH,
*

*>> Brian
*

*>>
*

*>> On 10/05/2017 02:36 PM, Sadegh Faramarzi Ganjabad wrote:
*

*>>
*

*>>> Hello,
*

*>>>
*

*>>> I am running a test FEP simulation to calculate free energy of the
*

*>>> ionization of an amino acid inside a membrane protein. Here is the FEP part
*

*>>> of my namd config.
*

*>>>
*

*>>> source ../tools/fep.tcl
*

*>>>
*

*>>> alch on
*

*>>> alchType FEP
*

*>>> alchFile all-ion-beta.pdb
*

*>>> alchCol B
*

*>>> alchOutFile forward-shift-pr.fepout
*

*>>> alchOutFreq 10
*

*>>> alchBondDecouple on
*

*>>> alchBondLambdaEnd 1.0
*

*>>>
*

*>>> alchVdwLambdaEnd 1.0
*

*>>> alchElecLambdaStart 0.5 #soft potential
*

*>>> alchVdWShiftCoeff 6.0
*

*>>> #alchDecouple off
*

*>>>
*

*>>> alchEquilSteps 100
*

*>>> set numSteps 500
*

*>>>
*

*>>> runFEPmin 0.0 1.0 0.0625 10000 1000 310
*

*>>>
*

*>>> Then I used ParseFEP of VMD. The difference between DeltaG of the
*

*>>> forward and backward transformation is about 5 kcal/mol for lambda=0 to
*

*>>> 0.5, and it become almost 0 for lambda = 0.6 to 1. I should probably
*

*>>> increase simulation time for each lambda from 10,000 to say 10,000,000
*

*>>> until the plots of forward and backward lie on top of each other. My
*

*>>> question is that is this the only criterion for convergence of FEP
*

*>>> calculation? How can I make sure my simulation is long enough?
*

*>>>
*

*>>> Also, if I use thermodynamic integration method for free energy
*

*>>> calculations, what would be convergence criteria for that?
*

*>>>
*

*>>> Thanks,
*

*>>> Sadegh
*

*>>>
*

*>>>
*

*>> --
*

*>> Brian Radak
*

*>> Postdoctoral Appointee
*

*>> Leadership Computing Facility
*

*>> Argonne National Laboratory
*

*>>
*

*>> 9700 South Cass Avenue, Bldg. 240
*

*>> <https://maps.google.com/?q=9700+South+Cass+Avenue,+Bldg.+240&entry=gmail&source=g>
*

*>> Argonne, IL 60439-4854
*

*>> (630) 252-8643
*

*>> brian.radak_at_anl.gov
*

*>>
*

*>
*

*>
*

*> --
*

*> Brian Radak
*

*> Postdoctoral Appointee
*

*> Leadership Computing Facility
*

*> Argonne National Laboratory
*

*>
*

*> 9700 South Cass Avenue, Bldg. 240
*

*> <https://maps.google.com/?q=9700+South+Cass+Avenue,+Bldg.+240&entry=gmail&source=g>
*

*> Argonne, IL 60439-4854
*

*> (630) 252-8643
*

*> brian.radak_at_anl.gov
*

*>
*

**Next message:**Brian Radak: "Re: convergence criterion of free energy perturbation (FEP) simulations for pKa calculation"**Previous message:**Brian Radak: "Re: convergence criterion of free energy perturbation (FEP) simulations for pKa calculation"**In reply to:**Brian Radak: "Re: convergence criterion of free energy perturbation (FEP) simulations for pKa calculation"**Next in thread:**Brian Radak: "Re: convergence criterion of free energy perturbation (FEP) simulations for pKa calculation"**Reply:**Brian Radak: "Re: convergence criterion of free energy perturbation (FEP) simulations for pKa calculation"**Messages sorted by:**[ date ] [ thread ] [ subject ] [ author ] [ attachment ]

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