AMBER Archive (2008)

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

From: Carlos Simmerling (carlos.simmerling_at_gmail.com)
Date: Wed Jul 09 2008 - 08:37:36 CDT

look at these and the articles referenced

Geney, R., Layten, M., Gomperts, R., Hornak, V. and Simmerling, C.,
"Investigation of salt bridge stability in a Generalized Born solvent
model", J. Chem. Theory Comput., 2:115, 2006.

Okur, A., Wickstrom, L. and Simmerling, C., "Evaluation of salt bridge
structure and energetics in peptides using explicit, implicit and
hybrid solvation models", J. Chem. Theory Comput., 4:288, 2008

On Wed, Jul 9, 2008 at 5:37 AM, <guardiani_at_fi.infn.it> wrote:
> 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.
>>>
>>>
>>> ----------------------------------------------------------------
>>> This message was sent using IMP, the Internet Messaging Program.
>>>
>>>
>>> -----------------------------------------------------------------------
>>> The AMBER Mail Reflector
>>> To post, send mail to amber_at_scripps.edu
>>> To unsubscribe, send "unsubscribe amber" (in the *body* of the email)
>>> to majordomo_at_scripps.edu
>>>
>>
>>
>>
>> --
>> ===================================================================
>> 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
>> ===================================================================
>> -----------------------------------------------------------------------
>> The AMBER Mail Reflector
>> To post, send mail to amber_at_scripps.edu
>> To unsubscribe, send "unsubscribe amber" (in the *body* of the email)
>> to majordomo_at_scripps.edu
>>
>
>
>
> ----------------------------------------------------------------
> This message was sent using IMP, the Internet Messaging Program.
>
>
> -----------------------------------------------------------------------
> The AMBER Mail Reflector
> To post, send mail to amber_at_scripps.edu
> To unsubscribe, send "unsubscribe amber" (in the *body* of the email)
> to majordomo_at_scripps.edu
> 

-- 
===================================================================
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
===================================================================
-----------------------------------------------------------------------
The AMBER Mail Reflector
To post, send mail to amber_at_scripps.edu
To unsubscribe, send "unsubscribe amber" (in the *body* of the email)
      to majordomo_at_scripps.edu