Aliphatic Index
Calculate the aliphatic index of protein sequences to assess thermostability
What is the Aliphatic Index?
The Aliphatic Index is a measure of the relative volume occupied by aliphatic amino acid side chains (alanine, valine, isoleucine, and leucine) in a protein sequence. It serves as a positive factor for predicting the thermostability of globular proteins.
Introduced by Atsushi Ikai in his 1980 paper in The Journal of Biochemistry, this index emerged from statistical analysis showing that proteins from thermophilic bacteria have significantly higher aliphatic indices than ordinary proteins. The aliphatic index has since become a standard protein parameter for assessing thermal stability.
How does the Aliphatic Index work?
The aliphatic index is calculated by summing the mole percentages of aliphatic amino acids, weighted by their relative side chain volumes:
Where , , , and are the mole percentages (100 × mole fraction) of alanine, valine, isoleucine, and leucine respectively.
Side chain volume coefficients
The coefficients represent the relative volume of each aliphatic side chain compared to alanine:
| Amino Acid | Coefficient | Rationale |
|---|---|---|
| Alanine (A) | 1.0 | Reference side chain (implicit) |
| Valine (V) | 2.9 | Side chain ~2.9× the volume of alanine |
| Isoleucine (I) | 3.9 | Side chain ~3.9× the volume of alanine |
| Leucine (L) | 3.9 | Side chain ~3.9× the volume of alanine |
These coefficients were derived from the relative volumes of aliphatic side chains as determined by Ikai's analysis of globular protein structures.
Interpreting the results
Higher aliphatic index values indicate greater thermostability potential. Typical ranges vary by protein type:
- < 65: Low aliphatic content, typical for many mesophilic proteins
- 65–85: Moderate aliphatic content, common for globular proteins
- 85–105: High aliphatic content, often seen in thermostable proteins
- > 105: Very high aliphatic content, characteristic of thermophilic organisms
Proteins from thermophilic bacteria and archaea consistently show elevated aliphatic indices compared to their mesophilic counterparts. This correlation makes the aliphatic index useful for identifying thermostable variants during protein engineering.