I also suggest carefully viewing and analyzing the MD trajectory. It's very
easy to try to use restraints to make a large structure change but have it
get tangled up along the way. Restraints are much better at maintaining a
structure than at creating one.
On Nov 4, 2016 10:41 AM, "Kasprzak, Wojciech (NIH/NCI) [C]" <
kasprzaw.mail.nih.gov> wrote:
> Dr. Simmerling,
>
> Thank you for the pointers. The initial single-stranded RNA form is
> coiled, but not A-form.
> That is why I started from a wide energy well range (say -69.0 +/- 40' deg
> for the alpha),
> but with the force constants no higher than the 32.0 shown in the sample
> input. I will focus on the
> force specs first. For a stretch of 6 nts (all backbone angles) to which
> the etstraints were applied
> the "RESTRAINTS" value reported in the out file varied approximately from
> 1.0 to 15.0.
> Since I never used the dihedral restraints before, I am not sure if it's
> too high or too low.
>
> Thank you again, Voytek Kasprzak
>
> Wojciech (Voytek) Kasprzak (Contractor)
> Analyst Programmer,
> Basic Science Program,
> Leidos Biomedical Research, Inc.
> Frederick National Laboratory for Cancer Research (FNLCR)
> Frederick, MD 21702
> (301) 846 5537
> http://binkley2.ncifcrf.gov/users/kasprzak
>
> ________________________________________
> From: Carlos Simmerling [carlos.simmerling.gmail.com]
> Sent: Friday, November 04, 2016 10:10 AM
> To: AMBER Mailing List
> Subject: Re: [AMBER] RNA backbone dihedral restraints question
>
> I'm not clear on what you're doing. Do the restraint target values match
> the initial structure? If not, how high are the initial energies? you might
> also consider making the initial values match the input structure, then
> changing the target values over time to match the desired structure. this
> avoids the high penalties that can come with severe mismatch. also keep in
> mind that the restraint force constants are in radians, so if you are
> getting low penalty energies but it isn't matching your target values, you
> might want to increase the force constants.
>
> On Fri, Nov 4, 2016 at 10:05 AM, Kasprzak, Wojciech (NIH/NCI) [C] <
> kasprzaw.mail.nih.gov> wrote:
>
> > Dear Amber Users,
> >
> > I have been trying to temporarily force a single-stranded fragment of a
> > larger RNA in
> > a GB neck2 protocol simulation into a proper A-form (half) helix geometry
> > using backbone
> > dihedral angle restraints shown below (illustrated for only one
> > nucleotide). I employed several
> > different four point (r1 .. r4) ranges around the ideal A-form values
> (+/-
> > 70' down to +/-2'
> > illustrated below), but despite seeing that restraints are being used
> > (non-zero values listed in
> > in the MD output file), the actual angles measured by cpptraj dihedral
> > command vary a lot, and
> > the single stranded fragment turns from bad to worse (dramaticaly bending
> > in all directions)
> > in just 10 ns of MD simulation.
> >
> > Am I missing something fundamental in the restraints specifications? If
> > the restraints are
> > defined correctly, what else should I look for? Is there any
> > other/simpler way to force a
> > single-stranded RNA fragment into A-form backbone geometry?
> > (If you need more data from me, please let me know)
> >
> > Sample backbone angle restraints for one RNA nucleotide (G4) employed in
> > test runs:
> >
> > # 4 GUA ALPHA: (3 DA O3')-(4 DG P)-(4 DG O5')-(4 DG C5') -71.0 -67.0
> > around -69.0 deg
> > &rst iat = 96, 97, 100, 101,
> > r1 = -72.0, r2 = -71.0, r3 = -67.0, r4 = -66.0,
> > rk2 = 32.0, rk3 = 32.0,
> > &end
> > # 4 GUA BETA: (4 DG P)-(4 DG O5')-(4 DG C5')-(4 DG C4') 170.1 174.1
> > around 172.1 deg
> > &rst iat = 97, 100, 101, 104,
> > r1 = 169.1, r2 = 170.1, r3 = 174.1, r4 = 175.1,
> > &end
> > # 4 GUA GAMMA: (4 DG O5')-(4 DG C5')-(4 DG C4')-(4 DG C3') 54.5 58.5
> > around 56.5 deg
> > &rst iat = 100, 101, 104, 124,
> > r1 = 53.5, r2 = 54.5, r3 = 58.5, r4 = 59.5,
> > &end
> > # 4 GUA DELTA: (4 DG C5')-(4 DG C4')-(4 DG C3')-(4 DG O3') 80.8 84.8
> > around 82.8 deg
> > &rst iat = 101, 104, 124, 129,
> > r1 = 79.8, r2 = 80.8, r3 = 84.8, r4 = 85.8,
> > &end
> > # 4 GUA EPSILN: (4 DG C4')-(4 DG C3')-(4 DG O3')-(5 DA P) -160.7
> > -156.7 around -158.7 deg
> > &rst iat = 104, 124, 129, 130,
> > r1 = -161.7, r2 = -160.7, r3 = -156.7, r4 = -155.7,
> > &end
> > # 4 GUA CHI: (4 DG O4')-(4 DG C1')-(4 DG N9)-(4 DG C4) -73.8 -69.8
> > around -71.8 deg
> > &rst iat = 106, 107, 109, 123,
> > r1 = -74.8, r2 = -73.8, r3 = -69.8, r4 = -68.8,
> > &end
> >
> > Best regards, Voytek Kasprzak
> >
> >
> > Wojciech (Voytek) Kasprzak (Contractor)
> > Analyst Programmer,
> > Basic Science Program,
> > Leidos Biomedical Research, Inc.
> > Frederick National Laboratory for Cancer Research (FNLCR)
> > Frederick, MD 21702
> > (301) 846 5537
> > http://binkley2.ncifcrf.gov/users/kasprzak
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
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Received on Tue Nov 08 2016 - 04:00:02 PST
