We
present a thermodynamic argument showing that the evaporation
and condensation free-energy barriers of water confined between two
hydrophobic self-assembled monolayers (SAMs) vary more gradually with
the SAM hydrophobicity as compared to the case of water confined between
two bare hydrophobic surfaces (no SAMs). We validate our theory by
calculating the free-energy profiles of water confined between two
SAMs and between two bare surfaces of different hydrophobicities.
An implication of our findings is the existence of three regimes of
stability of confined water as a function of the hydrophobicity of
the SAMs. In comparison to bare planar surfaces with no SAMs, the
highly hydrophobic SAMs act to stabilize the liquid state, whereas
weakly hydrophobic SAMs stabilize the vapor state of confined water.
For intermediate hydrophobicities, the SAMs reduce both the evaporation
and the condensation free-energy barriers. These results imply that
the effects of SAM hydrophobicity on the behavior of confined water
are nontrivial and richer than previously thought.
Glycogen
synthase kinase 3 β (GSK3β) is a serine/threonine
kinase that phosphorylates several protein substrates in crucial cell
signaling pathways. Owing to its therapeutic importance, there is
a need to develop GSK3β inhibitors with high specificity and
potency. One approach is to find small molecules that can allosterically
bind to the GSK3β protein surface. We have employed fully atomistic
mixed-solvent molecular dynamics (MixMD) simulations to identify three
plausible allosteric sites on GSK3β that can facilitate the
search for allosteric inhibitors. Our MixMD simulations narrow down
the allosteric sites to precise regions on the GSK3β surface,
thereby improving upon the previous predictions of the locations of
these sites.
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