On Sat, Feb 15, 2014 at 7:01 AM, Rajesh Kumar <rajesh444.gmail.com> wrote:
> Hi,
>
> I am working on DNA duplex models with subsitutued benzene rings. When I
> calculated the binding free energies for the duplex formations (say strand
> A and complimetary strand B), I got comparable values for MMGBA and MMPBSa
> outputs. But the E(El) and E(GBor PB) values are very high but with
> opposite signs and are of very closer in magnitude.
>
I would expect this. Bear in mind that nucleic acids are highly charged
as each residue carries a -1 total charge. As a result, I would expect
the gas phase electrostatic energy to be dominated by the
phosphate-phosphate repulsion and be highly unfavorable. Other
interactions are unimportant compared to the size of these interactions.
This (correctly) indicates that DNA duplexes are highly unstable in
vacuum. We know, however, that DNA duplexes are highly stable in solution,
which is a direct result of the solvation free energy (more than)
compensating for the repulsive gas-phase electrostatic interactions. The
first Amber tutorial actually walks you through a series of calculations
that demonstrate this effect.
So the numbers here suggest that DNA duplexes are stable precisely because
of its highly favorable solvation free energy.
My questions:
>
> [1] How do we interpret these values EEL of 1453.4885 and EGB of
> -1445.0181 (or EPB of 1444.5930).
>
I hopefully answered this above.
> As negative sign indicates repulsive interactions, EEL of 1453.4885 shows a
> repulsive binding energy for the formation of DNA duplex from its strands.
> So it means solvation stabilzes the DNA duplex. Am I right?
>
A negative energy indicates attractive interactions. Other than that this
statement is correct.
Also wen I replaced with more number of benzene rings with A-T pairs in the
> duplex, I expected there will be loss of electrostatic interactions as the
> subsituted benzene rings cannot form a strong hydrogen bonds. Again EEl and
> EGB are similar magniude with opposite sign.
>
EEL and EGB or EPB are very often compensatory, as the solvent stabilizes
unfavorable charge interactions. Also, hydrogen bonding in DNA/RNA confer
selectivity, not stability. What I mean by this is that the hydrogen bonds
are not nearly strong enough to "glue" the nucleic acid residues together
-- it is the solvation forces that do this. Instead, these hydrogen bonds
act as discriminatory features that slightly destabilize non-WC pairings
over canonical WC pairings (a number I recall from one of my graduate
courses is ~5 kcal/mol per pair). Therefore, I would expect the EEL and
EGB numbers to differ very little from the loss of base pair hydrogen
bonds, as their values are (still) dominated by the interactions of the
phosphates.
HTH,
Jason
--
Jason M. Swails
BioMaPS,
Rutgers University
Postdoctoral Researcher
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Received on Sat Feb 15 2014 - 08:30:02 PST
