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15 N backbone dynamics of the S‐peptide from ribonuclease A in its free and S‐protein bound forms: Toward a site‐specific analysis of entropy changes upon folding
Author(s) -
Alexandrescu Andrei T.,
RathgebSzabo Klara,
Jahnke Wolfgang,
Schulthess Therese,
Kammerer Richard A.,
Rumpel Klaus
Publication year - 1998
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560070220
Subject(s) - conformational entropy , chemistry , entropy (arrow of time) , peptide bond , ribonuclease , peptide , protein folding , crystallography , protein structure , residue (chemistry) , configuration entropy , thermodynamics , physics , rna , molecule , biochemistry , organic chemistry , gene
Abstract Backbone 15 N relaxation parameters (Rl, R2, 1 H‐ 15 N NOE) have been measured for a 22‐residue recombinant variant of the S‐peptide in its free and S‐protein bound forms. NMR relaxation data were analyzed using the “model‐free” approach (Lipari & Szabo, 1982). Order parameters obtained from “model‐free” simulations were used to calculate 1 H‐ 15 N bond vector entropies using a recently described method (Yang & Kay, 1996), in which the form of the probability density function for bond vector fluctuations is derived from a diffusion‐in‐a‐cone motional model. The average change in 1 H‐ 15 N bond vector entropies for residues T3‐S15, which become ordered upon binding of the S‐peptide to the S‐protein, is ‐12.6 ± 1.4 J/mol.residue.K. 15 N relaxation data suggest a gradient of decreasing entropy values moving from the termini toward the center of the free peptide. The difference between the entropies of the terminal and central residues is about ‐ 12 J/mol.residue.K, a value comparable to that of the average entropy change per residue upon complex formation. Similar entropy gradients are evident in NMR relaxation studies of other denatured proteins. Taken together, these observations suggest denatured proteins may contain entropic contributions from non‐local interactions. Consequently, calculations that model the entropy of a residue in a denatured protein as that of a residue in a di ‐ or tri‐peptide, might over‐estimate the magnitude of entropy changes upon folding.