Dear Francois,
Thank you for the suggestion. I have a couple of other questions about
using the building block approach as you suggested. What exactly do you
mean by "design this BD and the charge constraints used during the charge
fitting step..."? I'm planning on performing MD simulations of taxol with
PEG of different lengths linked with a few different photoaffinity labels.
Is this approach more efficient than recalculating the charges for each
large molecule? I think that I would probably just be breaking up the
molecule into three parts: taxol, the PEG chain, and the photo affinity
label. Would that method be acceptable or should I try to break up the
molecule even further?
Also, I have another question related to what I'm doing at the moment. I'm
on the second step of tutorial
B4<
http://ambermd.org/tutorials/basic/tutorial4b/>and the calculation
has been running for over 3 hours on my desktop (Fedora
v15, Intel Core i5 2500K (3.3GHz), and 16 GB RAM) and it's still going.
I've checked the sqm.out file several times over the past hour and it
hasn't moved beyond 1250 iterations. I don't know if this is normal or if I
incorrectly set one of the parameters. I'll attach the most recent sqm.out
file. I'm trying to generate parameters for the structure that I attached
in previous emails.
Thanks everyone,
Matt
On Thu, Nov 3, 2011 at 4:34 AM, FyD <fyd.q4md-forcefieldtools.org> wrote:
> Dear Matthew,
>
> > Well, I don't exactly know how small/big a molecule should be to be
> > considered medium. To give you an idea the taxol derivative that I am
> > working with has 147 atoms without hydrogen atoms added.
>
> I did not follow your questions & just looked at your structure. This
> looks like two organic drugs (one is taxol) connected by a linker of
> polyethyleneglycol PEG http://en.wikipedia.org/wiki/Polyethylene_glycol.
>
> If you consider this molecule as a single molecule during charge
> derivation the conformation you will get after geometry optimization
> will not be representative. We have used PEG linkers of different
> lengths and for sure the PEG linker does not stay linear during MD
> simulations...
> See http://q4md-forcefieldtools.org/images/cbc.jpg
>
> Instead, I would like to suggest you to use (i) R.E.D.
> Server/Ante_R.E.D. 2.0 and (ii) R.E.D. Server/R.E.D. IV and to follow
> the building block approach. In this procedure, you split the big
> molecule into elementary building blocks (BD). In your case you could
> consider at least four BD.
>
> - See http://q4md-forcefieldtools.org/REDS/
> - The tutorial: http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php
> - Example of R.E.DD.B. project with PEG linker of different length;
> http://q4md-forcefieldtools.org/REDDB/projects/F-84/
> PMID: http://www.ncbi.nlm.nih.gov/pubmed/20549756
>
> The advantage of this BD approach are:
> - each BD has a well defined conformation and is not 'randomly' chosen.
> - cpu time for geometry optimization is far shorter
> - In your case a key point in that you can easily define different
> lengths for the linker (polymer of EG)... i.e. different analogs for
> your initial/big structure.
>
> The main limitation of this BD approach is that you have to design
> this BD and the charge constraints (intra- and inter-molecular charge
> constraints in your case) used during the charge fitting step to
> generate the _molecular fragments_ used to reconstruct the initial/big
> molecule. This is not obvious when one first starts, but we can help
> you for that; the approach to follow in your case is quite basic...
> See once again http://q4md-forcefieldtools.org/REDDB/projects/F-84/
> you will find all what you need there (obviously your case is not a
> glycoconjugate).
>
> You will find other features in R.E.D. Server as well:
> - Add hydrogens to your structure
> http://q4md-forcefieldtools.org/REDS/faq.php#19
> - create a totally new structure
> http://q4md-forcefieldtools.org/REDS/faq.php#20
> - correct a bad input geometry:
> http://q4md-forcefieldtools.org/REDS/faq.php#18
>
> regards, Francois
>
>
>
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>
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Received on Sun Nov 06 2011 - 19:00:03 PST
