AMBER Archive (2008)

Subject: Re: AMBER: Force fields for REMD with GB solvent

From: guardiani_at_fi.infn.it
Date: Wed Jul 09 2008 - 04:37:43 CDT

Thank you very much for your help. I will use the ff99SB
force field with both igb-5 and igb-7 and I will analyze
the differences.

I had never heard of the ion-pairing problem in GB models.
Could you please recommend some literature references ?

Best regards,

              Carlo Guardiani

Quoting Carlos Simmerling <carlos.simmerling_at_gmail.com>:

> we recently posted a detailed tutorial for REMD in amber10,
> you might want to look at that.
>
> you are right that the GB models introduce helical bias,
> much more so with HCT than OBC, which is more reasonable.
> however, we also showed that igb-7 (neck GB) is probably biased
> slightly against all secondary structures. as of now there is no "perfect"
> choice, and igb of 5 or 7 (with the appropriate radii) is probably
> the best choice. if the results depend strongly on the GB model between
> these two, then there is likely not a strong conformational preference
> anyway. ff99 is not good, I recommend ff99SB.
> also keep on the watch for ion pairing, particularly with Arg,
> which is also a known issue with many, if not most GB models.
> keep in mind that simulations in explicit solvent may well take hundreds
> of nanoseconds to converge, so differences between your results and
> the explicit solvent MD need to be done only in the context of
> well defined precision limits for data from the difference solvent models.
>
>
> On Tue, Jul 8, 2008 at 12:24 PM, <guardiani_at_fi.infn.it> wrote:
>> Dear Amber experts,
>>
>> I am currently performing REMD simulations in implicit solvent of
>> a peptide whose coordinates were taken from a larger protein.
>> My goal is to determine the equilibrium structure of the free
>> peptide in physiologic conditions. The peptide is first minimized
>> according to:
>>
>> Minimization
>> &cntrl
>> imin = 1,
>> maxcyc = 500,
>> ncyc = 250,
>> ntb = 0,
>> igb = 1,
>> gbsa = 1,
>> saltcon = 0.2,
>> cut = 300.0,
>> ntpr = 10,
>> ntx = 1,
>> /
>>
>> The minimized structure is then cloned into 12 replicas (12 corresponds
>> to the square root of the number of atoms in my peptide). The target
>> temperatures of the replicas are chosen in geometric progression and
>> are: 310, 332, 355, 380, 406, 435, 465, 498, 533, 570, 610, 652.
>> Each replica is heated from 0 K to the corresponding target temperature
>> in this way:
>>
>> Equilibration
>> &cntrl
>> imin = 0,
>> cut = 24.0,
>> igb = 1,
>> gbsa = 1,
>> saltcon = 0.2,
>> nstlim = 500000,
>> dt = 0.001,
>> ntt = 3, gamma_ln = 1.0,
>> tempi = 0.0, temp0 = 310.0,
>> ntx = 1, irest = 0, ntb = 0,
>> nscm = 50,
>> ntpr = 100, ntwr = 100, ntwx = 100
>> /
>>
>>
>> I then perform 2.5 ns of REMD simulation that will be discarded in the
>> computation of energies and other properties of interest. The input
>> file for this part of the simulation is like this:
>>
>> MD run
>> &cntrl
>> imin = 0,
>> cut = 24.0,
>> igb = 1,
>> gbsa = 1,
>> saltcon = 0.2,
>> nstlim = 2500,
>> numexchg = 800,
>> dt = 0.001,
>> ntt = 3, gamma_ln = 1.0,
>> tempi = 310.0, temp0 = 310.0,
>> ntx = 5, irest = 1, ntb = 0,
>> nscm = 50,
>> repcrd = 0,
>> ntpr = 500, ntwr = 500, ntwx = 500
>> /
>>
>>
>> After that I perform other 30 ns of simulation through 3 restarts with
>> input files of this kind:
>>
>>
>> MD run
>> &cntrl
>> imin = 0,
>> cut = 24.0,
>> igb = 1,
>> gbsa = 1,
>> saltcon = 0.2,
>> nstlim = 2500,
>> numexchg = 4000,
>> dt = 0.001,
>> ntt = 3, gamma_ln = 1.0,
>> tempi = 310.0, temp0 = 310.0,
>> ntx = 5, irest = 1, ntb = 0,
>> nscm = 50,
>> repcrd = 0,
>> ntpr = 500, ntwr = 500, ntwx = 500
>> /
>>
>> My problem is that the equilibrium population is completely dominated by
>> helical structures, which is in disagreement with the simulation of some
>> colleague who is performin explicit-solvent simulations on the same peptide.
>>
>> Basically I think there are two main sources of error:
>>
>> 1) I used the ff99 force field without noticing that it introduces a bias
>> toward helical structures. I am now not sure which force field is more
>> convenient for my simulations. Do you recommend I should use the ff03
>> force field or rather the ff99SB force field, or maybe yet another one ?
>>
>> 2) I performed my simulations with the Hawkins, Cramer, Trular generalized
>> Born model (igb=1). However I have read a paper
>> (J. Chem. Theory Comput. Vol 3, No 1, pag 156-169, 2007)
>> where the authors report on a comparison of REMD simulations on Ala10
>> and they conclude that OBC-GB and HCT-GB introduce a strong bias for
>> alpha-helical conformations while the GBn method (igb=7) produces a
>> conformational population in better agreement with experimental data.
>> Do you think the GBn method is the best choice of GB model for my
>> simulations ? And which set of atomic radii (PBradii) do you recommend ?
>>
>>
>> I thank you very much for your help and I am looking forward to receiving
>> feedback from you.
>>
>> Best regards,
>>
>> Carlo Guardiani
>>
>>
>> PS: If you notice any mistake in the REMD protocol that I am using, please
>> tell me.
>>
>>
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>
>
>
> --
> ===================================================================
> Carlos L. Simmerling, Ph.D.
> Associate Professor Phone: (631) 632-1336
> Center for Structural Biology Fax: (631) 632-1555
> CMM Bldg, Room G80
> Stony Brook University E-mail: carlos.simmerling_at_gmail.com
> Stony Brook, NY 11794-5115 Web: http://comp.chem.sunysb.edu
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