From Protein Structure to Function with Bioinformatics.pdf

7 Predicting Protein Function from Surface Properties 169surrounding solvent, but unlike the previous definition, the solvent accessible surfaceis generated from the centre of the solvent probe as it rolls over the van derWaals surface. Because the SAS is defined using the centre of the solvent probe,the SAS of a given protein atom is proportional to the number of solvent moleculesthat could simultaneously be in contact with it. This distinction is fundamentalwhen dividing the surface based on property. By definition, the reentrant regions ofa molecular surface are not associated to one atom and have a property associatedwith two or more protein atoms. Any portion of the SAS is associated with only asingle protein atom (Fig. 7.1). This difference is important when assigning a propertyto regions of a surface, for example when defining the surface as polar/nonpolar.The molecular surface is less suitable for assigning properties to individualatoms of the protein surface; hence SAS has been more widely adopted for characterisingphysical/biological properties of protein surfaces. These properties will bediscussed in the following sections.7.2 Surface PropertiesFollowing the definition of the protein surface, it is then important to define whatthe important surface properties are. These can be chemical, physical or biological.The most widely used properties are briefly introduced.7.2.1 HydrophobicityPolar and non-polar atoms at the surface of a protein will interact with the surroundingsolvent in different ways. The hydrogen-bonds of polar water molecules arelargely satisfied by hydrogen-bond groups of polar atoms at the surface. Non-polaratoms cannot form the same bonds. This difference in interaction forms the basis forthe hydrophobic effect in aqueous solvents (Chothia and Janin 1975). Non-polarsurface is unattractive for water molecules because water molecules placed next toit cannot form the same number of hydrogen-bonds as in bulk solution. As a consequencethe water molecules will arrange themselves into a semi-stable network tooptimise the hydrogen bonding between themselves. This ordering provides a drivingforce to minimise the contact with non-polar surface, whereby changes in thenon-polar surface area of solutes are related to the free energy of processes in solutionwith the unique properties of the molecular surface giving rise to differenceswith respect to the solvent accessible surface in modelling the hydrophobic effect(Jackson and Sternberg 1993). The free energy associated with this process is thegreatest stabilising force in determining the structure of globular proteins (whichtypically have a fairly hydrophobic core and polar surface). The effect is also significantas a driving force in the association of molecules. The hydrophobicity of a proteinsurface is thus a key property in function prediction.