Mitochondrial targeting sequences why ‘non‐amphiphilic’ peptides may still be amphiphilic

The notion that mitochondrial targeting peptides form amphiphilic α‐helices with one apolar and one polar, positively charged face is controversial, since some experimental results seem to imply that non‐amphiphilic targeting peptides can also function as import signals. However, the standard methods used to assess the amphiphilicity of a peptide may be misleading, since they do not take the flexibility of the amino acid side chains into account. To demonstrate this, we have developed a new method for calculating the amphiphilicity of helical peptides.