Biomedical Engineering Reference
In-Depth Information
The interface area, although clearly an important parameter in predicting biological
interfaces, was shown to be less dominant here than in other approaches, and
assumes a role that is complementary to the more detailed geometrical descriptors
of the interface.
Solvation properties. Molecular recognition is often mediated by water molecules
bound between the partners; such molecules contribute to lowering the potential
energy of the system through hydrogen bonding and van der Waals interactions.
In Sect. 1.2.4 , we have seen how to identify the interfacial water molecules and the
AW −BW interface. Interestingly, the connected components of this interface allow
one to single out different hydration patterns, from isolated water molecules to large
networks of interfacial water [ 16 ]. The connected components of the AB interface
correspond to previously identified binding patches [ 17 ], which are themselves
connected to the decomposition of the whole interface into modules of amino-
acids [ 55 ].
However, the affinity measures the difference in free energy between the complex
itself and the unbound proteins. Indeed, association is accompanied by desolvation
of the regions of the unbound protein surfaces that will become the protein-protein
interface. Affinity predictions have been investigated in two directions. First, the
power diagram has been used to characterize the protein-water interface in general.
A technical comment is in order here concerning the difficulties faced by Voronoı
models to handle large or unbounded cells, which arise in this case if the solvent
structure is undefined—this situation is common, for the model of a protein structure
does not in general specify the solvent structure unambiguously. While the sole
Voronoı diagram cannot cope with such uncertainty, information contained in the
α -shape allows restriction of these cells [ 16 ]. Of course, crystal structures typically
do feature many first-shell water molecules. Gerstein and Chothia [ 28 ] thus used
the power diagram to calculate both protein and solvent atomic densities at protein-
water interfaces in crystals, which showed a volume increase of protein atoms near
the interface together with a corresponding volume reduction in the solvating water.
Shape information was also incorporated, notably in the dependence of the densities
on the concave or convex regions in the protein surface. Second, models of binding
patches have been used to investigate the correlations between structural parameters
and dissociation free energies. In [ 45 ], the weighted average of the shelling order of
the atoms of the binding patch has been shown to outperform all other contenders
to predict the binding affinities of the binding affinity benchmark [ 39 ].
On the morphology of an interface: core and rim models. An important topic
when analyzing interfaces consists of unraveling the relationship between the
morphology of an interface and its biological and biophysical properties.
Simple geometric concerns coupled with residue conservation analyses of a
database of biological protein-protein complexes of known structure led Chakrabarti
and Janin [ 17 ] to suggest that biological protein-protein interfaces are organized
into a rim , consisting of residues for which all atoms are to some degree accessible
to solvent, and the core , consisting of residues in which any atom is fully buried.
Residue composition of the core region was observed to be significantly different
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