Protein Structure and Function. Application of Bioinformatics Methods - John Rigden 2014

Protein Function Prediction via Surface Properties
Surface Properties
Electrostatic Properties

The Specific features of electrostatic potential distribution on a molecular surface determine the Specificity of many interactions taking place there. These features are shaped by METABOLISM/18.html">The Influence of all atoms in the molecule, rather than just those lying on its surface. The attraction of opposite charges is one of the driving forces behind specific interactions. For instance, Proteins that bind to DNA and RНК typically feature several positively charged Amino Acids capable of interacting with the negatively charged phosphate groups of the nucleic acid backbone. The MetJ Transcription factor from E.coli also exploits the dipole moment of a positively charged a-helix to enhance its DNA binding affinity (Garvie and Phillips 2000). The enzyme superoxide dismutase exhibits a significant charge gradient within its near-surface volume, which accelerates The formation of a productive complex. Unlike most Enzymes, the rate-limiting step in converting the superoxide radical into a safe form is its non-covalent binding to the enzyme rather than the subsequent chemical reaction (Getzoff et al. 1983).

The simplest measure of Structure/110.html">Electrostatic Surface potential is given by Coulomb's law, which defines the potential at a point On the surface as the sum of the charges of surrounding protein atoms, normalized by their distance and the Dielectric Constant of the medium. More sophisticated atomic-level modeling, without explicitly including Water molecules, can be performed using the Poisson-Boltzmann equation (Fogolari et al. 2002). It accounts for water implicitly by employing an approximation of solvent effects on biomolecular interactions in solutions of varying Ionic strength. Several software packages, such as DelPhi, can be used to numerically solve this equation for Biomolecules (Rocchia et al. 2002). The resulting electrostatic potential can be mapped onto the protein surface using molecular graphics software.