2.6 Roles of Electrostatic Interaction in Aqueous Solution …
19
the extreme N-terminal peptide region of a tumor suppressor protein p53 (p53NTD)
[24], for example, the quantities being discussed are as follows (T = 298 K):
Decrease in ES component of conformational energy ~−514k B T,
ES component of energetic dehydration penalty ~537k B T,
Decrease in vdW component of conformational energy ~−108k B T,
vdW component of energetic dehydration penalty ~95k B T.
Though these quantities are quite large, the sum of the two ES components is
only ~23k B T, and the sum of the two vdW components is only ~−13k B T. The sum
of all the ES and vdW components is positive and as small as ~10k B T. These quantities were calculated using our state-of-the-art theoretical method where molecular
models are adopted for water, the structures of biomolecules (the MDM2-p53NTD
complex and isolated MDM2 and p53NTD) are treated at the atomic level, and the
structural fluctuation of the biomolecules in water are taken into account with the
aid of molecular dynamics (MD) simulations with all-atom potentials [22, 24] (see
Chap. 6 for more details). Therefore, the calculated values are quantitatively reliable.
We emphatically remark that by a dielectric continuum model of water, the entropic
EV effect cannot be taken into consideration and the energetic dehydration penalty
is not calculable with quantitative accuracy.
In aqueous solution under the physiological condition (water containing NaCl
at a concentration of ~ 0.15 mol/L), the electrostatic interaction is screened by not
only water molecules but also cations and anions. As a consequence, it becomes
over two orders of magnitude weaker and much shorter-ranged than in vacuum
[25]. The entropic interaction mentioned above, which originates from the translational displacement of water molecules, is significantly stronger than the screened
electrostatic interaction.
In a biological self-assembly process, charged portions in a biomolecule or
biomolecules are driven to become buried by the water-entropy effect. For the contact
of oppositely charged portions to occur upon the burial, the barrier due to the energetic dehydration penalty mentioned above must be overcome. It is overcome by
a large gain of water entropy. The contact of oppositely charged portions is quite
important, but it does not work as a significant driving force in a microscopic selfassembly process. Unfortunately, this is not well recognized in the biophysical and
biochemical research communities.
2.7 Translational, Configurational Entropy of Water
Leading Receptor-Ligand Binding and Protein Folding
A receptor-ligand binding (binging of two solute molecules), a good example of
biological self-assembly processes, is accompanied by a water-entropy gain and a
loss of conformational entropy of solute molecules (see Fig. 2.8b). However, the
gain is significantly larger than the loss [23, 24, 26]. For the binding of MDM2
19
the extreme N-terminal peptide region of a tumor suppressor protein p53 (p53NTD)
[24], for example, the quantities being discussed are as follows (T = 298 K):
Decrease in ES component of conformational energy ~−514k B T,
ES component of energetic dehydration penalty ~537k B T,
Decrease in vdW component of conformational energy ~−108k B T,
vdW component of energetic dehydration penalty ~95k B T.
Though these quantities are quite large, the sum of the two ES components is
only ~23k B T, and the sum of the two vdW components is only ~−13k B T. The sum
of all the ES and vdW components is positive and as small as ~10k B T. These quantities were calculated using our state-of-the-art theoretical method where molecular
models are adopted for water, the structures of biomolecules (the MDM2-p53NTD
complex and isolated MDM2 and p53NTD) are treated at the atomic level, and the
structural fluctuation of the biomolecules in water are taken into account with the
aid of molecular dynamics (MD) simulations with all-atom potentials [22, 24] (see
Chap. 6 for more details). Therefore, the calculated values are quantitatively reliable.
We emphatically remark that by a dielectric continuum model of water, the entropic
EV effect cannot be taken into consideration and the energetic dehydration penalty
is not calculable with quantitative accuracy.
In aqueous solution under the physiological condition (water containing NaCl
at a concentration of ~ 0.15 mol/L), the electrostatic interaction is screened by not
only water molecules but also cations and anions. As a consequence, it becomes
over two orders of magnitude weaker and much shorter-ranged than in vacuum
[25]. The entropic interaction mentioned above, which originates from the translational displacement of water molecules, is significantly stronger than the screened
electrostatic interaction.
In a biological self-assembly process, charged portions in a biomolecule or
biomolecules are driven to become buried by the water-entropy effect. For the contact
of oppositely charged portions to occur upon the burial, the barrier due to the energetic dehydration penalty mentioned above must be overcome. It is overcome by
a large gain of water entropy. The contact of oppositely charged portions is quite
important, but it does not work as a significant driving force in a microscopic selfassembly process. Unfortunately, this is not well recognized in the biophysical and
biochemical research communities.
2.7 Translational, Configurational Entropy of Water
Leading Receptor-Ligand Binding and Protein Folding
A receptor-ligand binding (binging of two solute molecules), a good example of
biological self-assembly processes, is accompanied by a water-entropy gain and a
loss of conformational entropy of solute molecules (see Fig. 2.8b). However, the
gain is significantly larger than the loss [23, 24, 26]. For the binding of MDM2