Re: [AMBER] MMPBSA results for DNA-ligand system

From: Josh Berryman <the.real.josh.berryman.gmail.com>
Date: Mon, 17 Jun 2013 10:14:47 +0200

My guess is that your code and params are fine, but that the underlying
physics of a continuum approximation is giving some problems. MMPBSA with
DNA is a tricky proposition due to the (somewhat) structured nature of the
water and salt shells around the molecule: at least, that is my own
experience from a quick study on the B/Z transition, which admittedly
happens at rather higher ionic strengths than you are looking at (M, not
mM). If netropsin itself is multiply charged, then that won't be helping.
 A few more second opinions you can get are:

1) Do a GBSA calculation: the approximation to the PB equation which GB
carries out isn't actually too bad, and this is easy to do.
2) Try using a fresh download of delPhi with default params instead of
whatever is bundled with AMBER.
3) Try calling it through NAB instead of mmpbsa.py
4) Try some kind of TI approach, this will be expensive but I guess at UCSD
you have plenty of CPU time, right?

Josh


On 17 June 2013 21:21, <deeptinayar.gmail.com> wrote:

>
> Sent from my BlackBerry® smartphone from !DEA
>
> -----Original Message-----
> From: "Sorensen, Jesper" <jesorensen.ucsd.edu>
> Date: Mon, 17 Jun 2013 05:33:48
> To: AMBER Mailing List<amber.ambermd.org>
> Reply-To: AMBER Mailing List <amber.ambermd.org>
> Subject: [AMBER] MMPBSA results for DNA-ligand system
>
> Hi Amber experts,
>
> I have calculated the PB energies for the binding process between DNA and
> Netropsin. However, I am getting some curious results that I'd like to
> understand more and I'd like to hear if any of you have ideas?
> I calculated these using PBSA stand-alone (see numbers below). Radii were
> MBONDI, the remaining details are in the PBSA input options below.
>
> 1) The results below are calculated with and without salt concentration.
> However, the results are very close to each other. I have compared the
> results with other codes (e.g. APBS) and they get values diverging 8-10
> kcal/mol due to the salt effect.
>
> 2) I have calculated the results using different grid resolutions
> (focusing was turned off), yet the results don't really display what I
> expected in terms of convergence behavior, but instead just fluctuate
> around the same range of values. Is this the expected behavior for PBSA?
>
> Any insight would be really helpful.
>
> Best regards,
> Jesper
>
>
> Salt concentration = 100mM (istrng=100.000000)
> GridRes dEPB
> .15 1202.3177
> .20 1201.9713
> .25 1201.9845
> .30 1202.5554
> .35 1202.2611
> .40 1202.0522
> .45 1202.2218
> .50 1201.9514
> .55 1202.4602
> .60 1201.7396
> .65 1200.5449
> .70 1200.9878
> .75 1201.1727
> .80 1200.8361
> .85 1199.6109
> .90 1201.1486
> .95 1203.6329
> 1.0 1202.2278
>
> Salt concentration = 0 mM
> GridRes dEPB
> .15 1201.9931
> .20 1200.3285
> .25 1200.1105
> .30 1200.4338
> .35 1200.0356
> .40 1200.5173
> .45 1201.1034
> .50 1201.0788
> .55 1201.0346
> .60 1200.3855
> .65 1199.6695
> .70 1200.2409
> .75 1201.1009
> .80 1200.4463
> .85 1199.1350
> .90 1201.1621
> .95 1203.6926
> 1.0 1202.1964
>
>
> PBSA input file:
>
> PBSA input
> &cntrl
> imin=0,
> ntx=1,
> ipb=1,
> inp=1,
> /
> &pb
> epsin=1.000000,
> epsout=80.000000,
> smoothopt=0,
> istrng=100.000000,
> pbtemp=300,
> radiopt=0,
> dprob=1.4,
> iprob=2.00,
> arcres=0.0625,
> npopt=0,
> solvopt=1,
> accept=0.001,
> maxitn=10000,
> fillratio=2,
> space=1.0,
> nbuffer=0,
> nfocus=1,
> fscale=8,
> npbgrid=1,
> bcopt=5,
> eneopt=2,
> frcopt=0,
> scalec=0,
> sasopt=0,
> saopt=0,
> cutfd=5,
> cutnb=0,
> nsnba=1,
> phiout=0,
> phiform=1,
> npbverb=1,
> sprob=1.4,
> rhow_effect=1.000,
> use_sav=0,
> cavity_surften=0.005420
> cavity_offset=-1.008000,
> maxsph=400
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Received on Mon Jun 17 2013 - 01:30:02 PDT
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