Date: Mon, 14 Jul 2003 20:46:06 -0600
From: "Thomas E. Cheatham, III"
Subject: AMBER: Re: methylphosphonate



> I am familiar only with MD simulation of unmodified DNA using Amber. I am
> using Amber 6 and I would like to do simulation of DNA modified by
> substituting one oxygen atom of phosphate group with methyl group, namely
> methylphosphonate. Could you please suggest me as follow?

To give you an idea of where to look, a very simple search of PubMed
(http://www.ncbi.nlm.nih.gov/entrez) will display a number of recent works
that used methyl-phosphonate modified DNA in MD simulation in both R+S
stereochemistry's. This simple search, along with working through the
various simple tutorials on the AMBER WWW page (such as the plastocyanin
tutorial), *should* be enough to suggest how to modify the standard
residues (located in the AMBER dat directories). If you still cannot
understand it, read through the manuals in a little detail and it should
become apparent.

To pull parameters from the literature, see papers by Ferguson/Kollman
Antisense Rev Dev 1, 243-254 (1991), Hamelberg et al. (NAR 30, 3615-3623
(2002), Kulinska et al (JBSD 15, 987-998 (1998)), in addition to the
numerous NMR and other experimental studies... The work by Hamelberg is
likely within the context of the parm94/99.dat force field's.
Alternatively, you can upgrade to AMBER7 and use GAFF/Antechamber to aid
in the development of these parameters.

Good luck with your simulations!

Thomas E. Cheatham, III (Assistant Professor) College of Pharmacy