Hello to Dr. Ross Walker and all the Amber list contributors,
Thank you for the thorough review of my GB protocol for a large
RNA structure. I implemented all the indicated changes (most importantly
moving to the Langevin thermostat), ran the equilibration for a total of 1ns and
followed with MD. Unfortunately, the final results are a slow-motion version
of the earlier structural failures, with the base pairs involving the 5' and 3'
nucleotides, in the middle of otherwise robust, all-paired helices ( can be
viewed as two stacked helices) opening first, followed by the failure of the
stacking (bending), rotations of the two halves around the connecting
backbone and slow flattening of the helices. If these are indicators of known
problems (with prep or GB itself), I would appreciate more information on it.
No such issues occur in the explicit solvent approach.
Dr. Walker commented that "GB will be terrible for highly polar systems such
as DNA / RNA," and my experience seems to second that. On the other hand,
GB protocol tutorial I read uses a small DNA fragment. Again, any enlightening
comments would be appreciated (say, good for small nucleic acid structures,
based on crystallography data, bad in other cases.)
Also, with a cutoff of 999, the GB execution speed (even with PMEMD) for
my 264nt RNA structure appears to be comparable to the explicit solvent
MD runs (on the order of 1ns of simulation time per day on a 24 core cluster),
as suggested by Dr. Walker.
Hope these observations help others and, maybe, provoke more discussion.
Best regards,
Voytek Kasprzak
Wojciech (Voytek) Kasprzak [Contractor]
Analyst Programmer,
Basic Science Program, SAIC-Frederick, Inc.
National Cancer Institute in Frederick, Frederick, MD
(301) 846 5537
www-lecb.ncifcrf.gov/~kasprzak
________________________________________
From: Ross Walker [ross.rosswalker.co.uk]
Sent: Thursday, September 22, 2011 12:30 PM
To: 'AMBER Mailing List'
Subject: Re: [AMBER] GB protocol problems for large RNAs
Hi Wojciech
> I am attempting to move from an explicit solvent protocol (working,
> but slow) to
> the GB simulations for large, multi-chain RNA structures (~260-300nt,
> with a diameter
> in excess of 120A), using Amber10 (sander.MPI).
I hate to be the bearer of bad news here but have you actually checked the
timings? For something this big GB will most likey (since you should set cut
much larger, ideally have no cut off at all [cut=9999.0]) be slower than
your implicit solvent calculations and also significantly less accurate. I
will let others comment more but my understanding is that GB will be
terrible for highly polar systems such as DNA / RNA. You would probably be
much better trying to improve the performance of your explicit solvent
calculations.
[...]
All the best
Ross
/\
\/
|\oss Walker
---------------------------------------------------------
| Assistant Research Professor |
| San Diego Supercomputer Center |
| Adjunct Assistant Professor |
| Dept. of Chemistry and Biochemistry |
| University of California San Diego |
| NVIDIA Fellow |
|
http://www.rosswalker.co.uk |
http://www.wmd-lab.org/ |
| Tel: +1 858 822 0854 | EMail:- ross.rosswalker.co.uk |
---------------------------------------------------------
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Received on Tue Sep 27 2011 - 07:30:03 PDT
