C. Micheletti, G. Lattanzi and A. Maritan
Elastic
properties of proteins: Insight on the folding process and
evolutionary selection of native structures
J. Mol. Biol. 321, 909-921 (2002).
Link to online article.
ABSTRACT
We carry out a theoretical study of the vibrational and
relaxation proper-ties of naturally occurring proteins with the
purpose of characterizing both the folding and equilibrium
thermodynamics. By means of a suitable model, we provide a full
characterization of the spectrum and eigenmodes of vibration at
various temperatures by merely exploiting the knowledge of the protein
native structure. It is shown that the rate at which pertur-bations
decay at the folding transition correlates well with experimental
folding rates. This validation is carried out on a list of about 30
two-state folders. Furthermore, the qualitative analysis of residues
mean square dis-placements (shown to reproduce crystallographic data
accurately) provides a reliable and statistically accurate method to
identify crucial folding sites/contacts. This novel strategy is
validated against clinical data for human immunodeficiency virus type
1 (HIV-1) protease. Finally, we compare the spectra and eigenmodes of
vibration of natural proteins against randomly generated compact
structures and regular random graphs. The comparison reveals a
distinctive enhanced flexibility of natural structures accompanied by
slow relaxation times at the folding temperature. The fact that these
properties are connected intimately to the presence and assembly of
secondary motifs hints at the special criteria adopted by evolution in
the selection of viable folds.