C. Micheletti, P. Carloni and A. Maritan
Accurate and efficient description of protein vibrational
dynamics: comparing molecular dynamics and
Gaussian models
Proteins, 55, 635 (2004).
Link to online article.
ABSTRACT
Current all-atom potential based molecular dynamics (MD) allow the
identification of a protein's functional motions on a wide-range of
time-scales, up to few tens of ns. However, functional large scale motions
of proteins may occur on a time-scale currently not accessible by
all-atom potential based molecular dynamics. To avoid the massive
computational effort required by this approach several simplified
schemes have been introduced. One of the most satisfactory is the
Gaussian Network approach based on the energy expansion in terms of
the deviation of the protein backbone from its native
configuration. Here we consider an extension of this model which
captures in a more realistic way the distribution of native
interactions due to the introduction of effective sidechain
centroids. Since their location is entirely determined by the protein
backbone, the model is amenable to the same exact and computationally
efficient treatment as previous simpler models. The
ability of the model to describe the correlated motion of protein
residues in thermodynamic equilibrium is established through a series
of successful comparisons with an extensive (14 ns) MD simulation
based on the AMBER potential of HIV-1 protease in complex with a
peptide substrate. Thus, the model presented here emerges as a
powerful tool to provide preliminary, fast yet accurate
characterizations of proteins near-native motion.