Dear Matthew,
> 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..."?
Charge derivation when using R.E.D. can be decomposed in three steps:
See
http://onlinelibrary.wiley.com/doi/10.1002/jcc.540161106/abstract
&
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918240/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918240/figure/F1/
(i - QM step) geometry optimization (by QM by using Gaussian, GAMESS
or Firefly) of entire molecule(s) (a molecular fragment by itself does
not exist in QM)
(ii - QM step) molecular electrostatic potential(s) MEP(s) computation
(by QM by using Gaussian, GAMESS or Firefly) of the optimized
geometry(ies) obtained in step (i)
(iii - empirical step) charge fitting by using the RESP program for
the entire molecule(s) based on the MEP(s) obtained in step (ii) AND
(if required) design of molecular fragment(s) (an empirical model
where the notion of molecular fragment(s) makes sense; i.e. a FF
library to be used with an empirical FF).
This means that during the charge fitting step (iii) one can add
specific charge constraints to define charge values for molecular
fragment(s) based on MEP computation for entire molecule(s) obtained
by QM.
For instance in your case:
R.E.D.
Me-OCH2CH2-OH -----> fragment OCH2CH2 + fragment OCH2CH2-OH
<-> <->
a single intra-molecular charge constraint = 0 for Me + OH groups of EG
(see RESP manual .
http://q4md-forcefieldtools.org/RED/resp/)
Then, in LEaP, the fragments OCH2CH2 & OCH2CH2-OH can be used to
polymerize EG into PEG (the next version of R.E.D. will directly
generate oligomeric structures):
LEaP
OCH2CH2 + OCH2CH2-OH -----> (OCH2CH2)n-OCH2CH2-OH
Other possibilities between two molecules in your case:
R.E.D. LEaP
RaO-Me + HO-Rb -----> fragment RaO + fragment Rb --> RaO-Rb (ether)
<------->
inter-molecular charge constraint = 0 for Me of molecule 1 & OH group
of molecule 2 (see RESP manual .
http://q4md-forcefieldtools.org/RED/resp/)
and
R.E.D. LEaP
RaCOO-Me + HO-Rb -----> fragment RaCOO + fragment Rb --> RaCOO-Rb (ester)
<------->
inter-molecular charge constraint = 0 for Me of molecule 1 & OH group
of molecule 2.
See the tutorials for more examples:
http://q4md-forcefieldtools.org/Tutorial/Tutorial-1.php
http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php
> I'm planning on performing MD simulations of taxol with
> PEG of different lengths linked with a few different photoaffinity labels.
Yes, this is what I understood when I first saw this PEG: EG can be
polymerized into various length of PEG ;-)
> 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?
You have no idea about the conformation of PEG - so I would use the
molecule Me-OCH2CH2-OH (see above) from which the conformation is well
defined (you could use two conformation RESP fit for instance for this
building block; see
http://q4md-forcefieldtools.org/REDDB/projects/F-84/mol1.pdb) and
build PEG based on an EG fragment which is polymerized in LEaP...
> 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.
You are optimizing a structure which is very flexible; the
conformation you are going to generate will not be representative; I
simply think that it does not make sense. We do not use the
semi-empirical sqm code . q4md-forcefieldtools.org. My understanding
is that sqm should provide a quick result (semi-empirical is always
faster to QM). If not, I guess there is a convergence problem - likely
because your structure is flexible; or because your input structure is
not good/accurate.
regards, Francois
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Mon Nov 07 2011 - 07:30:07 PST
