  The spectrum and scale of fluctuations in protein structures affect the range
of cell phenomena, including stability of protein structures or their
fragments, allosteric transitions and energy transfer. The study presents a
statistical-thermodynamic analysis of relationship between the sequence
composition and the distribution of residue fluctuations in protein-protein
complexes. A one-node-per residue elastic network model accounting for the
nonhomogeneous protein mass distribution and the inter-atomic interactions
through the renormalized inter-residue potential is developed. Two factors, a
protein mass distribution and a residue environment, were found to determine
the scale of residue fluctuations. Surface residues undergo larger fluctuations
than core residues, showing agreement with experimental observations. Ranking
residues over the normalized scale of fluctuations yields a distinct
classification of amino acids into three groups. The structural instability in
proteins possibly relates to the high content of the highly fluctuating
residues and a deficiency of the weakly fluctuating residues in irregular
secondary structure elements (loops), chameleon sequences and disordered
proteins. Strong correlation between residue fluctuations and the sequence
composition of protein loops supports this hypothesis. Comparing fluctuations
of binding site residues (interface residues) with other surface residues shows
that, on average, the interface is more rigid than the rest of the protein
surface and Gly, Ala, Ser, Cys, Leu and Trp have a propensity to form more
stable docking patches on the interface. The findings have broad implications
for understanding mechanisms of protein association and stability of protein
structures.
