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

Predicting Protein Function from Surface Properties
Surface Properties
Hydrophobicity

Following the definition of protein surfaces, it is essential to determine which of their properties are significant for research. These may include chemical, biological, or physical characteristics. Below is a Brief Overview of the most widely used Structure/108.html">Surface Properties.

Polar and nonpolar atoms on a protein surface interact with the surrounding solvent in different ways. The tendency of polar Water molecules to form Hydrogen Bonds is primarily satisfied by the polar atoms on the protein surface. Nonpolar atoms cannot form hydrogen bonds, and this difference is the driving force behind the hydrophobic effect In aqueous solutions (Chothia and Janin 1975). The interaction of water molecules with a nonpolar protein surface is energetically unfavorable because molecules adjacent to such a surface cannot form as many hydrogen bonds as water molecules in the bulk solvent. As a result, the water molecules near the surface form a semi-rigid network to optimize hydrogen bonding among themselves. This ordering acts as a driving force for water to minimize contact with the nonpolar surface; consequently, Changes in the nonpolar surface area of solute molecules are directly related to the Free energy of processes in solution. It is important to note that, due to its construction specifics, using the molecular surface introduces distortions when modeling the hydrophobic effect compared to using the Solvent-accessible surface. The free energy associated with this process is the primary stabilizing factor in determining the Introduction/12.html">Structure of Globular Proteins, which typically feature a Hydrophobic core and a polar surface. The hydrophobic effect is also crucial as a driving force in molecular interactions. Thus, protein surface hydrophobicity is a key property for predicting its function.

The simplest measure of hydrophobicity is the sum of exposed polar and nonpolar surface areas, though other, more sophisticated Definitions exist. These equate the hydrophobicity of individual atom types to solvation energy derived from experimental sources or characteristic Cell/13.html">Protein Structure Databases. A standard approach treats solvation energy as a function of two variables: the decrease in the accessible surface area and the observed transfer energy of the corresponding atoms. The transfer energy of a given molecule represents The change in free energy when moving it between two different environments. When considering Protein Interactions, the most suitable representation of this transfer is the movement of Amino Acids from water to octanol, which mimics the interior of a protein (Fauchere and Pliska 1983). Transfer energy values also exist for other pairs of media that serve as end states in alternative physical processes: vapor-water (Wolfenden et al. 1981) and cyclohexane-water (Radzicka et al. 1988). Alternatively, the Atomic Solvation Potential (ASP) can be used, with values optimized by comparing differences in transfer energies between native protein structures and deliberately misfolded models (Wang et al. 1995). These derived values are frequently employed in protein folding calculations and molecular docking Methods.