Re: AMBER: GB versus explicit medium

From: Carlos Simmerling <>
Date: Mon, 24 Nov 2008 06:08:40 -0500

Using GB to replace explicit water already has some weaknesses, but I
think GB with dielectric of ~80 is an even worse model for the
interior of a lipid..
I'm not sure if that is the problem, but I would not really expect
this to work. Charlie Brooks has used his GB for membranes, but they
define a dielectric boundary at the water/lipid interface. There is a
review article on this in ARCC.

in order to make the GB vs explicit comparison that you did below, you
really need to compare the same system, not a comparison where ones
has many more restraints.

On Mon, Nov 24, 2008 at 4:39 AM, Francesco Pietra <> wrote:
> Hi all:
> Is any experience in carrying out long MD simulations for
> transmembrane proteins under both GB conditions and explicit
> environment?
> This question because I am carrying out MD with a large transmembrane
> protein, composed of several identical units and carrying a docked
> small protein (docked in accordance with physiological data) in the
> extracellular part. MD under GB conditions after a careful
> minimization and heating to 300K. Force field ff99SB.
> MD under GB at 300K
> with restraint on Cl-
> using pmemd in amber10
> &cntrl
> imin=0, irest=1, ntx=5, ntb=0,
> ig=-1, igb=5, nrespa=2, ntc=2,
> ntf=2, ntt=3, gamma_ln=2.0,
> nstlim=30000, dt=0.002,
> ntpr=100, ntwx=100,
> tempi=300.0, temp0=300.0,
> cut=999.0, rgbmax=999.0,
> ntr=1,
> /
> Keep Cl- 427 restrained
> 32.0
> RES 427
> I understand that, forced by the huge system, I am using rather
> drastic conditions (dt=0.002, nrespa=2), though I was badly surprised
> to see the initial portion of one of the chains of the pore region
> undergoing a 90 degrees bent at SER 14 (14 from the beginning of the
> chain, while the chain continues for ca 23 amino acids in the pore
> region). EPTOT EKTOT and ETOT remain constant. The extracellular
> portion and docked small protein also undergo some conformational
> adjustment, though, no "distortion" of the system occurs.
> In another approach, for different reasons, I isolated the pore region
> (with a small molecule docked in; docked in accordance with
> physiological data)), cutting away the extracellular portion and
> restraining the ends of the chains at the end of the pore region.
> Under periodic conditions, in a hydrated POPC membrane, for a much
> longer MD than the above, no distortion of the pore region occurred
> Production MD, restraining
> capping groups
> &cntrl
> imin=0, irest=1, ntx=5,
> nstlim=100000, dt=0.002,
> cut=10, ntb=2, ntp=1, taup=2.0,
> ntc=2, ntf=2,
> ntpr=1000, ntwx=1000,
> ntt=3, gamma_ln=2.0,
> temp0=300.0,
> ntr=1,
> /
> Keep ACE 79 restrained
> 32.0
> RES 79
> many other capping groups restrained.
> I wonder whether this may be a limitation of GB or there is evidence,
> or suspicion, that setting up was not adequate. Surely, if the GB
> simulation has to be made some fold slower that it is, the simulation
> could hardly be carried out for an adequate time.
> Thanks
> francesco pietra
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Received on Fri Dec 05 2008 - 16:32:50 PST
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