From Protein Structure to Function with Bioinformatics.pdf

170 N.J. Burgoyne and R.M. JacksonThe simplest measure of hydrophobicity is a simple sum of exposed polar andnon-polar surface area, but other more sophisticated measures exist. These equatethe hydrophobicity of individual atom types to solvation energies derived fromexperimental sources or databases of representative protein structures. A commonapproach is to treat the energy of solvation as a function of the loss in SAS areaand the observed transfer energies of the atoms involved. The transfer energy of agiven molecule is the free energy change derived from moving the moleculebetween two different environments. Where protein interactions are concerned themost applicable reference states come from moving each amino acid betweenwater and octanol (used as a proxy to the interior of a protein) (Fauchere andPliska 1983). However, values for the transfer between other different environmentsalso exist, which act as reference states for other physical processes:vapour-water (Wolfenden et al. 1981), cyclohexane-water (Radzicka et al. 1988).Alternatively, Atomic Solvation Potential (ASP) values are optimised by comparingthe energy difference between the structures of native proteins and deliberatelymis-folded decoy proteins (Wang et al. 1995). The derived values have been usedin protein folding and docking simulations.7.2.2 Electrostatics PropertiesThe electrostatic character of a molecular surface determines the specificity of manyof the interactions that are made at the surface of the protein. This character is influencedby atoms that occur throughout the whole molecule not just by those that lie onthe surface. Charge complementarity is one of the drivers for a specific interaction.For example, the proteins that bind DNA and RNA typically have a number of positivelycharged residues that can associate with the negatively charged sugar-phosphatebackbone. The E. coli transcription factor MetJ also uses positively charged α-helixdipole moments to enhance binding to the DNA (Garvie and Phillips 2000). Theenzyme superoxide dismutase has a steep charge gradient across its surface whichenhances the rate of productive complex formation. Unlike the majority of enzymes,the rate-limiting step of making the superoxide radical ion safe is the speed of bindingrather than the chemical reaction that follows (Getzoff et al. 1983).The simplest measure of an electrostatic surface potential is given by Coulomb’slaw. This describes the potential at a surface point as the sum of the charges on surroundingatoms in the protein, weighted by their distance and dielectric characterof the intervening medium. More sophisticated modelling at an atomistic levelwithout the explicit inclusion of water molecules can be done using the Poisson-Boltzman equation (Fogolari et al. 2002). It models water implicitly, using anapproximation of the effects of solvent on the interactions of biomolecules in solutionsof different ionic strength. Several computer programs can be used to numericallysolve the equation for biomolecules e.g. DelPhi (Rocchia et al. 2002). Theresulting electrostatic potential can be displayed at the protein surface using anumber of molecular graphics programs.