AMBER Archive (2009)

Subject: Re: [AMBER] R.E.D intra-mcc and reorientation

From: Ganesh Krishnan (hereisganesh_at_yahoo.com)
Date: Sat Jul 11 2009 - 17:56:18 CDT

Dear Francois,

Thanks a lot for taking the time to answer my questions. Also, I would like to thank the R.E.D team for making the tasking of deriving reliable partial charges remarkably painless.

Regards,

Ganesh Krishnan
Yingling Group
NC State University

________________________________
From: FyD <fyd_at_q4md-forcefieldtools.org>
To: amber_at_ambermd.org
Cc: sleone_at_rics.bwh.harvard.edu; q4md-fft_at_q4md-forcefieldtools.org
Sent: Saturday, July 11, 2009 4:05:56 AM
Subject: Re: [AMBER] R.E.D intra-mcc and reorientation

Dear Ganesh,

> I am interested in partial charge derivation of a polymer. I am using R.E.D III for this. I have a few questions regarding the set up:
>
> 1) I decided to derive the partial charge of one monomer and use those charges for each constituent monomer in the polymer. I was wondering if people could comment on the advantages and disadvantages of this procedure.

You are right this is a key question: The basis of the answer is the work of Kollman's group published in 1995 by Cieplak et al. Application of the multimolecule and multiconformational RESP methodology to biopolymers: Charge derivation for DNA, RNA, and proteins. J. Comput. Chem. 1995, 16, 1357-1377.

The basic idea behind this work is instead of computing the charges for a (big) polymer such a polypeptide, polysaccharide or oligonucleotide (that cannot be handled by quantum mechanics because too big, anyway), to derive charges for the repeating units constituting the polymer.

The advantages:
- You are indeed able to derive the charges for macrosystems based on building block units & force field topology database (FFTopDB) building: this is the basis of _ALL_ empirical force fields nowadays.
- You can potentially build any type of macrostructures using this approach; See for instance:
http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php
http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#22
http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#27
  and
http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#26 for an organo-glycoconjugate.
- You rigorously control the conformation(s) of each unit used in charge derivation (conformations does affect charge values based on MEP computation).
- When deriving charge for large structures you often select the conformation based on luck/random_?. I do not like the idea of luck deciding for me ;-)

The disadvantages:
- The procedure appears complex for new users. (R.E.D. has been develop for this purpose to make the work of Cieplak et al. more accessible to new users. We have written several tutorials to help as well. See http://q4md-forcefieldtools.org/Tutorial/)
- When generating the building block units, constraints during the charge fitting step for "connecting group(s)" are introduced. Here, if you do not know which chemical group you want to use as a connecting group, you will introduce errors in the fitting step (that are difficult to judge/quantify). R.E.D. IV incorporate now a statistics module to solve this problem. This new feature will be first released through R.E.D. Server (soon).

> 2) Since a monomer is a fragment and not a complete molecule, I "artificially" satisfied the valence by bonding it to other groups. I then set an intra-mcc to derive charges only for the relevant fragment. As I understand, this is in accordance with the R.E.D III tutorial (http://q4md-forcefieldtools.org/Tutorial/Tutorial-1.php#10). I was curious as to how the choice of the group selected to satisfy the valence will affect the partial charge.
> eg. Let us say the polymer is (-CH2-)n. I derive partial charges for CH3-CH2-CH3 with intra-mcc on both CH3s. Would this provide accurate and useful partial charges? What factors would govern the choice of the chosen group (CH3 in this case)?

You are 100 % right... Once again the publication by Cieplak et al. should provide you a starting point for your polymer.
Our http://q4md-forcefieldtools.org/Tutorial/ tutorials should help also. R.E.DD.B. has been totally rebuilt; we will submit new projects that will present examples different from proteins & nucleic acids.
Finally, we can provide you private assistance for your project as well, if you use the "Help" service available from R.E.D. Server.

Your CH3-CH2-CH3 case is "ridiculously" small, but perfectly well chosen. "ridiculously" because too small, but is a perfect example because you need to exclude the two CH3 chemical groups to construct a polymer of CH2s i. e. (CH2)n. In this case, using INTRA-MCCs set to zero for these 2 methyl groups should work and introduce small errors during the fitting step...

> 3) Regarding RBRA reorientation (http://q4md-forcefieldtools.org/Tutorial/Tutorial-1.php#3), I was wondering if the choice of the 3 atoms is arbitrary. In other words, can I choose any 3 atoms within my molecule for the reorientation procedure?

You are right once again: Nothing else to say. Now you could select:
- only heavy atoms,
- heavy atoms common to all the units constituting your polymer,
- more generally if you reorient once using the atoms "1 2 3", we always reorient the same structure a second time using "3 2 1": This allows cancelling out the (small) effect of the 1st orientation by the 2nd orientation. This was clearly quantified for the dimethylphophate molecule for instance when building the nucleic acid FFTopDB.

Thanks for this discussion. May be Piotr would like to add something...

regards, Francois

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