Dear Ilya,
> Could you please suggest,
> what is the best way to obtain parameters for this molecule?
> tyrosine-O-(PO2)-O-CH2-5'ribose
> this is my first non-protein/non-nucleic MD.
The first approach is to use the "whole molecule approach" i.e. use
the whole molecule tyrosine-O-(PO2)-O-CH2-5'ribose in charge
derivation. I do not think this approach is a good choice because the
conformation involved in charge derivation will not be representative
and it will be mainly based on luck or lack of luck...
Instead, you could use the building block approach where your
input/'big' molecule is split into elementary building blocks.
Considering that the phosphate group has a negative charge and to
avoid unwanted interactions that would occur in gas phase between this
negative charge and the NH backbone of Tyr and/or the hydroxyl groups
of ribose, you could define three elementary building blocks:
- Tyrosine or tyrosine dipeptide (ACE-TYR-NME if you want to generate
the central fragment of Tyr; i.e. to connect the Tyr residue within a
protein).
- Dimethylphosphate Me-O-PO2-O-Me (or Ethylmethylphosphate - to be tested)
- Ribose
You will define two inter-molecular charge constraints (INTER-MCC
keyword in a p2n file) between each methyl group of Dimethylphosphate
and the hydroxyl group of Tyrosine and the 5'-hydroxyl group of ribose.
- This approach cannot be performed with the R.E.D. III.51 tools; you
could use R.E.D. Server/R.E.D. IV instead.
- You execute R.E.D. Server/Ante_R.E.D. 2.0 to generate the P2N files
for your three building blocks. Pay attention to break chemical
equivalencing if you use Dimethylphosphate or use Ante_R.E.D. 1.x from
the R.E.D. III.51 tools.
- You modify the TITLE and TOTAL-CHARGE in the P2N file when required
- You add two INTRA-MCC in the corresponding P2N file for the ACE &
NME capping groups if the Tyrosine dipeptide is used.
See
http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#15
- You add two INTER-MCC in the 1st P2N file of the series of 3 P2N files.
The idea is highly similar to that used to build nucleotide fragments:
See
http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#26
However, here, the two INTER-MCC are between three building blocks and
not between only two.
- You end up with three FG1 fragments in the mol2 file format for the
3 P2N files in the Mol_MM directory. These three mol2 files have to be
associated in LEaP. I hope this step will be perform by R.E.D. in the
future.
The approach described is that presented in the F-90 R.E.DD.B. project:
http://q4md-forcefieldtools.org/REDDB/projects/F-90/
Considering that you have a glycopeptide, the next question is to
wonder which algorithm to involve in MEP computation, and which force
field to use. As your sugar unit is a ribose, I would select the
"RESP-A1A" charge model and use the Amber99SB force field (or a
corresponding/newer version) for the entire epitope; i.e. I would NOT
use GLYCAM. This means Amber values for 1-4 non-bonded interactions as
defined at:
http://q4md-forcefieldtools.org/REDDB/projects/F-85/ &
http://www.ncbi.nlm.nih.gov/pubmed/21792425?dopt=Abstract
I hope this helps.
regards, Francois
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Received on Tue Mar 06 2012 - 03:00:03 PST
