[gmx-users] Re: gromacs and pH description!

[Antonio Baptista]

On Tue, 30 Jan 2007, David van der Spoel wrote:

> Mark Abraham wrote:
>> Florian Haberl wrote:
>> 
>>>>  1) how can i explaine "pH" into my system ( consisting protein & Na+ 
>>>> ions
>>>> ) under gromacs? i'd like to reach to pH ~ 4.5 or 5 in my system.
>> 
>> What concentration of H+ ions are needed to get to these pH values? Can you 
>> do that in a system with 10^4 to 10^5 atoms? Even if you can, there are no 
>> MD water models that allow hydrogen atoms to dissociate freely, as happens 
>> in real water.
>> 
> This is not entirely correct, there are constant pH simulation models, 
> developed by Charlie Brooks and others where you can simulate transfer of 
> protons from one side chain to another. THis is not exactly what you need 
> here, and they only work in implicit solvent so far (and in Charmm at that). 
> I'd like to have such models implemented in gromacs, and with explicit 
> solvent. Anyone interested?

There are actually several constant-pH MD methods, some of them using 
explicit solvent. We have ourselves developed a constant-pH MD method 
based on stochastic protonation changes [J. Chem. Phys. (2002) 117:4184]. 
Although the method uses a Poisson-Boltzmann method to periodically change 
the protonation states, the MM/MD simulations are done with explicit 
solvent.

We have actually implementated this stochastic constant-pH MD method using 
Gromacs [J. Phys. Chem. B (2006) 110:2927], basically following a 
stop-and-go approach using bash and awk scripts to interface Gromacs with 
MEAD (a PB solver by Don Bashford) and MCRP (a in-house program for Monte 
Carlo sampling of protonation states). Unfortunately, the whole thing is 
still too messy and hard-wired at some places, which makes it unsuitable 
to be submitted as a contribution to Gromacs, at least for now.

Another explicit-solvent method, based only on MM/MD, was proposed by 
Hunenberger [J. Chem. Phys. (2001) 114:9706], but its theoretical basis 
seems to be wrong [J. Chem. Phys. (2002) 116:7766]. As far as I know, all 
other constant-pH MD methods proposed so far used indeed implicit solvent. 
Stochastic approaches using implicit solvent were used by McCammon [J. 
Comput. Chem. (2004) 25:2038] and by Antosiewicz [Phys. Rev. E (2002) 
66:051911], and we have also proposed a fractional-charge approach 
[Proteins (1997) 27:523] where implicit solvent was used for computational 
speed; all these methods depend on some sort of simplified 
electrostatics-oriented method (Poisson-Boltzmann, generalized Born, etc) 
to perform the protonation calculations. Implicit solvent was also used in 
a method proposed by Brooks [Proteins (2004) 56:738], following a 
different but theoretically vague approach to include protonation effects.

Antonio

--
Antonio M. Baptista
Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa
Av. da Republica, EAN, ITQB II, Apartado 127
2781-901 Oeiras, Portugal
phone: +351-214469619         email: baptista at itqb.unl.pt
fax:   +351-214411277         WWW:   http://www.itqb.unl.pt/~baptista
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>
> -- 
> David.
> ________________________________________________________________________
> David van der Spoel, PhD, Assoc. Prof., Molecular Biophysics group,
> Dept. of Cell and Molecular Biology, Uppsala University.
> Husargatan 3, Box 596,  	75124 Uppsala, Sweden
> phone:	46 18 471 4205		fax: 46 18 511 755
> spoel at xray.bmc.uu.se	spoel at gromacs.org   http://folding.bmc.uu.se
> ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
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--
Antonio M. Baptista
Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa
Av. da Republica, EAN, ITQB II, Apartado 127
2781-901 Oeiras, Portugal
phone: +351-214469619         email: baptista at itqb.unl.pt
fax:   +351-214411277         WWW:   http://www.itqb.unl.pt/~baptista
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