Re: AMBER: Essential ions and water molecules in MMPBSA computations

From: Jiri Sponer <>
Date: Mon, 12 Mar 2007 15:44:08 +0100 (MET)

Waters were included for DNA ligand binding in this work,

Molecular dynamics simulations and thermodynamics analysis of DNA-drug complexes. Minor groove binding between 4 ',6-diamidino-2-phenylindole and DNA duplexes in solution
Author(s): Spackova N, Cheatham TE, Ryjacek F, Lankas F, van Meervelt L, Hobza P, Sponer J
Source: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 125 (7): 1759-1769 FEB 19 2003

and it seemed to improve results, though the numbers are delicate.
Tom Cheatham will likely comment on it.

Myself, with the waters, I am not fully sure, there are open
issues and likely no perfect solutions. It likely will depend
on the exact nature of your hydration site. Short residency,
long residency, permanent, bridge, pocket, static, dynamical, rattling...

Just few systems with "essential" hydration sites and each hydration event
is absolutely different.
Trapped water molecules are essential to structural dynamics and function of a ribozyme
Rhodes MM et al.
  - internally hydrated cavity.

RNA kink-turns as molecular elbows: Hydration, cation binding, and large-scale dynamics
Razga F et al
Source: STRUCTURE 14 (5): 825-835 MAY 2006
       anharmonic molecular elbow mediated by dynamical water

Long-residency hydration, cation binding, and dynamics of loop E/helix IV rRNA-L25 protein complex
Author(s): Reblova K et al.
Source: BIOPHYSICAL JOURNAL 87 (5): 3397-3412 NOV 2004
             static close to permanent water bridges.

   If you have static water molecule bridging something I would
   probably try to formally include it as a "ligand" and compare
   the results with and without including this water, (using
   trajectory of the "complex").
   See what happens. A salient structural picture is not
   necessarily reflected by large free energy stabilization.

Best wishes, Jiri

[ Charset ISO-8859-1 unsupported, converting... ]
> I got the BIOPHYSICAL JOURNAL 85 (3): 1787-1804 SEP 2003 and it seems to answer my question related to the presence of an essential Na+ ion in complex with a receptor. Thank you.
> My next question was about the presence of an essential water molecule in the binding site. How would one go about inclusion of a very critical water molecule during enthalphy and entropy computations by MM-PSA ?
> my best regards,
> Jenk
> Jiri Sponer <> wrote: It has been done for example for quanine DNA quadruplexes,
> where monovalents are essential to stabilize this DNA
> It is possible and it works.
> Formation pathways of a guanine-quadruplex DNA revealed by molecular dynamics and thermodynamic analysis of the substates
> Author(s): Stefl R, Cheatham TE, Spackova N, Fadrna E, Berger I, Koca J, Sponer J
> Source: BIOPHYSICAL JOURNAL 85 (3): 1787-1804 SEP 2003
> Molecular dynamics simulations of guanine quadruplex loops: Advances and force field limitations
> Author(s): Fadrna E, Spackova N, Stefl R, Koca J, Cheatham TE, Sponer J
> Source: BIOPHYSICAL JOURNAL 87 (1): 227-242 JUL 2004
> best wishes, Jiri
> [ Charset ISO-8859-1 unsupported, converting... ]
> > Dear Amber community,
> >
> > I have such a complex system that one Na+ ion and two water molecules make a significant contribution to the stability of the complex and I personally wouldn't want to remove them during MMPBSA computations. I was wondering if any has succeeded including such essential ions and water molecules in MMPBSA computations. Can anyone please guide me on how this can be done and what outcome can be expected by MMPBSA for a complex system including ions and water molecules?
> >
> >
> > My best regards,
> >
> > Jenk
> >
> >
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Received on Wed Mar 14 2007 - 06:07:16 PDT
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