Prediction Of Peptide Structure: How Far Are We?

Rational design of peptides is a challenge, which would benefit from a better
knowledge of the rules of sequence-structure-function relationships. Peptide
structures can be approached by spectroscopy and NMR techniques but data from
these approaches too frequently diverge. Structures can also be calculated in
silico from primary sequence information using three algorithms: Pepstr, Robetta,
and PepLook. The most recent algorithm, PepLook introduces indexes for evaluating
structural polymorphism and stability. For peptides with converging experimental
data, calculated structures from PepLook and, to a lesser extent from Pepstr, are
close to NMR models. The PepLook index for polymorphism is low and the index for
stability points out possible binding sites. For peptides with divergent
experimental data, calculated and NMR structures can be similar or, can be
different. These differences are apparently due to polymorphism and to different
conditions of structure assays and calculations. The PepLook index for
polymorphism maps the fragments encoding disorder. This should provide new means
for the rational design of peptides.