Mapping the Hydropathy of Amino Acids Based on Their Local Solvation Structure

In
spite of its relevant biological role, no general consensus
exists on the quantitative characterization of amino acid’s
hydropathy. In particular, many hydrophobicity scales exist, often
producing quite different rankings for the amino acids. To make progress
toward a systematic classification, we analyze amino acids’
hydropathy based on the orientation of water molecules at a given
distance from them as computed from molecular dynamics simulations.
In contrast with what is usually done, we argue that assigning a single
number is not enough to characterize the properties of an amino acid,
in particular when both hydrophobic and hydrophilic regions are present
in a residue. Instead we show that appropriately defined conditional
probability densities can be used to map the hydrophilic and hydrophobic
groups on the amino acids with greater detail than possible with other
available methods. Three indicators are then defined based on the
features of these probabilities to quantify the specific hydrophobicity
and hydrophilicity of each amino acid. The characterization that we
propose can be used to understand some of the ambiguities in the ranking
of amino acids in the current scales. The quantitative indicators
can also be used in combination with standard bioinformatics tools
to predict the location of transmembrane regions of proteins. The
method is sensitive to the specific environment of the amino acids
and can be applied to unnatural and modified amino acids, as well as
to other small organic molecules.