AMBER Archive (2006)

Subject: Re: AMBER: Modify charges to increase/decrease hydrogen bond interaction

From: Thomas Cheatham (
Date: Mon Aug 14 2006 - 13:42:52 CDT

> I know that a specific residue (Ser) can form multiple hydrogen bonds with
> other residues in the same protein, which should help to form and stabilize
> a turn structure. Now I want to investigate the importance this hydrogen
> bond. The charge of oxygen atom in the hydroxyl group of Ser is -0.6546, and
> 0.4275 of hydrogen thereof. I plan to increase the charge of oxygen atom
> gradually to zero, and decrease the charge of hydrogen atom with the same
> quantity at the same time, and observe the hydrogen bond network of this Ser
> residue. This modification will be applied to the interaction between Ser
> and all other residues, but when the intra-residue interactions are
> evaluated, the charges remain the same as what amber force field gives. Does
> my research design make sense?

I am unclear as to why you want the "intra"- residue interactions to be
the same (noting that the 1-2, and 1-3 exclusions prevent the O--H from
interaction). The change in charge may well alter the torsional profiles
of the hydroxyl side chain but will likely have little effect on the

There are a couple of ways I might try to see the effect of the serine
(without any code modifications).

(1) Force the charge change via the thermodynamic integration facility to
perturb the charge in stages. This will allow you to "see" what effect
the change has on the conformational equilibria (noting that a change in
this equilibria will mean that a lot of sampling is required to have the
resulting free energies make any sense). This change in charge is easy
to watch, but how do you correlate this back to experiment?

(2) Instead, perturb the SER to ALA (both in the "unfolded" and hairpin
geometry so that you have a complete cycle). This is experimentally

\-/ Thomas E. Cheatham, III (Assistant Professor) College of Pharmacy
-/- Departments of Med. Chem. and of Pharmaceutics and Pharm. Chem.
/-\ Adjunct Asst Prof of Bioeng.; Center for High Performance Computing
\-/ University of Utah, 30 S 2000 E, SH 201, Salt Lake City, UT 84112
/-\ (801) 587-9652; FAX: (801) 585-9119
\-/ BPRP295A

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