48
M. P. Evstigneev and A. V. Shestopalova
(∆G el
solv
) and van der Waals (∆G vdW
solv
) desolvation, loss of H-bonds to-water (ΔN
solv
),
change in the number of translational (ΔG t ), rotational (ΔG r ), vibrational ( ∆G v
I
)
degrees of freedom, and restriction of internal rotations in MGB molecules (ΔG conf ).
The hydrogen bonding factor among the rest energy terms was shown to be more
important specifically for the MGB-ligands than for the intercalators [129].
The net energies in Eq. (2.4), which stabilize complexes, can be placed in descending order by the absolute value: ∆
∆
∆
G
G
G
hyd
v dW
pe
>
>
, whereas the order of
destabilizing factors is ∆
∆
∆
G
G
G
entr
HB
el
≥
>
[108].
With the aim of searching the physical factor the most strongly affecting the
binding affinity, the correlation coefficients of experimental energy with the solvation and intermolecular components for all the factors in Eq. (2.5) were calculated
[108]. It was found that the highest correlation is observed for the electrostatic energy, which suggests that the major effect on variation of DNA binding affinity with
the type of ligand is provided by the electrostatic component. This is in agreement
with the qualitative estimations of other authors [130, 131].
2.4.5 Energy Analysis of RNA Binding Reactions
Ligand binding with RNA is probably the most difficult object to study as compared
with DNA binding reactions due to large variability of RNA binding sites. In Ref.
[132] the energy analysis of binding of 11 small molecules to RNA aptamers was
accomplished using the methodology reviewed in section 2.4.2. Although the details of specific adaptation of the ligand to the binding site, currently considered to
be important in case of RNA binding ligands [133, 134], were not unveiled in this
work, the general patterns of distribution of energy over various energy terms were
reported to be similar to DNA intercalation and minor-groove binding, presumably
reflecting the general pattern of binding reactions in aqueous media [123, 129].
The most important contribution to the binding energetics in terms of the net
absolute energies in Eq. (2.4) is given by the ∆G hyd and ∆G vdW (∆
∆
G
G
hyd
v dW
>
)
factors, and the destabilization originates from ∆G entr and ∆G HB , which is qualitatively similar to what was found above for the DNA intercalation and minor-groove
binding. The electrostatic factor ∆G el is relatively unimportant for the ligands with
no charge or bearing single charge, whereas the doubly- or more-charged ligands
elevate ∆G el to the level commensurable with ∆G vdW .
The stabilizing energy terms in Eq. (2.5) can be placed in the sequence by extent of their contribution: ∆
∆
∆
G
G
G
vdW
im
hyd
v
II
>
>
. The sequence for the destabilizing energies is: ∆
∆
∆
G
G
G
vdW
solv
v
I
t r
≥
≥
, . The VDW energies were found to depend
strongly on the type and dimensions of side chains of the ligand and the efficacy of
π-stacking with RNA bases.
Intermolecular ( ∆G el
im
) and to-water (∆G el
solv
) electrostatic energies by the magnitude and sign strongly depend on the charge of the ligand, viz. ∆G el
im
is favourable
and ∆G el
solv
is unfavourable for positively charged ligands, whereas the signs of these
terms get reversed for negatively charged ligands.
M. P. Evstigneev and A. V. Shestopalova
(∆G el
solv
) and van der Waals (∆G vdW
solv
) desolvation, loss of H-bonds to-water (ΔN
solv
),
change in the number of translational (ΔG t ), rotational (ΔG r ), vibrational ( ∆G v
I
)
degrees of freedom, and restriction of internal rotations in MGB molecules (ΔG conf ).
The hydrogen bonding factor among the rest energy terms was shown to be more
important specifically for the MGB-ligands than for the intercalators [129].
The net energies in Eq. (2.4), which stabilize complexes, can be placed in descending order by the absolute value: ∆
∆
∆
G
G
G
hyd
v dW
pe
>
>
, whereas the order of
destabilizing factors is ∆
∆
∆
G
G
G
entr
HB
el
≥
>
[108].
With the aim of searching the physical factor the most strongly affecting the
binding affinity, the correlation coefficients of experimental energy with the solvation and intermolecular components for all the factors in Eq. (2.5) were calculated
[108]. It was found that the highest correlation is observed for the electrostatic energy, which suggests that the major effect on variation of DNA binding affinity with
the type of ligand is provided by the electrostatic component. This is in agreement
with the qualitative estimations of other authors [130, 131].
2.4.5 Energy Analysis of RNA Binding Reactions
Ligand binding with RNA is probably the most difficult object to study as compared
with DNA binding reactions due to large variability of RNA binding sites. In Ref.
[132] the energy analysis of binding of 11 small molecules to RNA aptamers was
accomplished using the methodology reviewed in section 2.4.2. Although the details of specific adaptation of the ligand to the binding site, currently considered to
be important in case of RNA binding ligands [133, 134], were not unveiled in this
work, the general patterns of distribution of energy over various energy terms were
reported to be similar to DNA intercalation and minor-groove binding, presumably
reflecting the general pattern of binding reactions in aqueous media [123, 129].
The most important contribution to the binding energetics in terms of the net
absolute energies in Eq. (2.4) is given by the ∆G hyd and ∆G vdW (∆
∆
G
G
hyd
v dW
>
)
factors, and the destabilization originates from ∆G entr and ∆G HB , which is qualitatively similar to what was found above for the DNA intercalation and minor-groove
binding. The electrostatic factor ∆G el is relatively unimportant for the ligands with
no charge or bearing single charge, whereas the doubly- or more-charged ligands
elevate ∆G el to the level commensurable with ∆G vdW .
The stabilizing energy terms in Eq. (2.5) can be placed in the sequence by extent of their contribution: ∆
∆
∆
G
G
G
vdW
im
hyd
v
II
>
>
. The sequence for the destabilizing energies is: ∆
∆
∆
G
G
G
vdW
solv
v
I
t r
≥
≥
, . The VDW energies were found to depend
strongly on the type and dimensions of side chains of the ligand and the efficacy of
π-stacking with RNA bases.
Intermolecular ( ∆G el
im
) and to-water (∆G el
solv
) electrostatic energies by the magnitude and sign strongly depend on the charge of the ligand, viz. ∆G el
im
is favourable
and ∆G el
solv
is unfavourable for positively charged ligands, whereas the signs of these
terms get reversed for negatively charged ligands.