Structure Fluctuations in Proteins and their Relationship to Amino Acid Propensities

Abstract

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 [1]. 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: (i) highly fluctuating - Gly, Ala, Ser, Pro and Asp, (ii) moderately fluctuating - Thr, Asn, Gln, Lys, Glu, Arg, Val and Cys (iii) weakly fluctuating - Ile, Leu, Met, Phe, Tyr, Trp and His. 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.1. A.M. Ruvinsky and I.A. Vakser. arXiv:0907.5021v1