Hi Vlad,
just short comment, besides restraints one can use HBfix potential
(we use it routinely now for RNA and protein-RNA systems to tune H-bonds
stability, also for noncanonical DNAs).
In contrast to restraints HBfix allows the H-bonds to be broken
and restored, i.e., it is a milder intervention compared to restraints.
Obviously, it does not resolve severely strained structures,
best wishes, Jiri
On Wed, 16 Feb 2022, Vlad Cojocaru wrote:
> Date: Wed, 16 Feb 2022 09:40:06 +0100
> From: Vlad Cojocaru <vlad.cojocaru.mpi-muenster.mpg.de>
> Reply-To: AMBER Mailing List <amber.ambermd.org>
> To: amber.ambermd.org
> Subject: Re: [AMBER] DNA breaking down during the simulation
>
> Dear Bogac,
>
> To me it sounds like this is not an imaging issue but rather bases flipping
> outwards if I understand it correctly. Does this happen close to the protein
> or in a region of DNA without protein contacts ? I also assume you do not
> talk about terminal bases either.
>
> We always use basepair restraints (the WC hbonds) as well as restraints of
> the well established protein-DNA contacts during large portions of the
> equilibration to make sure the DNA does not get distorted in any way and the
> protein-DNA interface relaxes well before letting everything free. This
> usually worked well for the systems we studied so far ....
>
> We have seen something similar when we modified DNA bases to study
> alternative DNA binding site sequences and did not use any restraints during
> equilibration ... But I assume you did not modify the sequence of your DNA
> ...
>
> Did you also checked carefully the conformation of the nucleotide in your
> starting structure ? We've seen that as well in structures, nucleotides
> flipped with distorted WC base pairing ....
>
> I am happy to help if you want to share with me an example stucture off the
> list ..
>
> Cheers
> Vlad
>
>
> On 2/16/22 00:26, b.ercig.nki.nl wrote:
>> Hello everyone,
>>
>>
>>
>> I am currently simulating a system which consists of 2 proteins and 1 dsDNA
>> in complex. I have made an production run of 10ns without any problems
>> however, when I extend the simulation after 10ns, I see that the
>> nucleotides in DNA strand is separating from the strand for some reason. I
>> am not sure if I was able to explain the situation. But this did not seem
>> to be a problem with starting structure to me, since the complex structure
>> was intact during the minimization, heating etc…
>>
>>
>>
>> I used Amber FF14SB forcefield together with BSC1 forcefield.
>>
>>
>>
>> solvateBox com TIP3PBOX 10.0 (also tried octahedral box; did not work also)
>>
>>
>>
>> and I neutralize the system using Na+; Cl- ions.
>>
>>
>>
>> Below is the parameters being used in the production run:
>>
>> imin=0,irest=1,ntx=5,
>>
>> nstlim=5000000,dt=0.002,
>>
>> ntc=2,ntf=2,ig=-1,
>>
>> cut=8.0, ntb=2, ntp=1, taup=2.0,
>>
>> ntpr=500, ntwx=500, ntwr = 500, ioutfm=1,
>>
>> ntt=3, gamma_ln=2.0,
>>
>> temp0=300.0,
>>
>>
>>
>> Maybe I am missing something really obvious here, and I would be really
>> happy to hear your feedbacks. Thanks all !
>>
>>
>>
>>
>>
>> Kind regards,
>>
>> Bogac Ercig
>>
>> Netherlands Cancer Institute
>>
>>
>> _______________________________________________
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>> AMBER.ambermd.org
>> http://lists.ambermd.org/mailman/listinfo/amber
>
> --
> Vlad Cojocaru, PD (Habil.), Ph.D.
> -----------------------------------------------
> Project Group Leader
> Department of Cell and Developmental Biology
> Max Planck Institute for Molecular Biomedicine
> Röntgenstrasse 20, 48149 Münster, Germany
> -----------------------------------------------
> Tel: +49-251-70365-324; Fax: +49-251-70365-399
> Email: vlad.cojocaru[at]mpi-muenster.mpg.de
> http://www.mpi-muenster.mpg.de/43241/cojocaru
>
>
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Received on Wed Feb 16 2022 - 01:00:03 PST
