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How stable is a collagen triple helix? An ab initio study on various collagen and β‐sheet forming sequences
Author(s) -
Pálfi Villő K.,
Perczel András
Publication year - 2008
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.20896
Subject(s) - collagen helix , triple helix , chemistry , crystallography , glycine , alanine , amino acid , supramolecular chemistry , proline , ab initio , hydroxyproline , peptide , stereochemistry , beta sheet , crystal structure , biochemistry , organic chemistry
Collagen forms the well characterized triple helical secondary structure, stabilized by interchain H‐bonds. Here we have investigated the stability of fully optimized collagen triple helices and β‐pleated sheets by using first principles ( ab initio and DFT) calculations so as to determine the secondary structure preference depending on the amino acid composition. Models composed of a total of 18 amino acid residues were studied at six different amino acid compositions: (i) L ‐alanine only, (ii) glycine only, (iii) L ‐alanines and glycine, (iv) L ‐alanines and D ‐alanine, (v) L ‐prolines with glycine, (vi) L ‐proline, L ‐hydroxyproline, and glycine. The last two, v and vi, were designed to mimic the core part of collagen. Furthermore, ii, iii, and iv model the binding and/or recognition sites of collagen. Finally, i models the G→A replacement, rare in collagen. All calculated structures show great resemblance to those determined by X‐ray crystallography. Calculated triple helix formation affinities correlate well with experimentally determined stabilities derived from melting point ( T m ) data of different collagen models. The stabilization energy of a collagen triple helical structure over that of a β‐pleated sheet is 2.1 kcal mol −1 per triplet for the [(‐Pro‐Hyp‐Gly‐) 2 ] 3 collagen peptide. This changes to 4.8 kcal mol −1 per triplet of destabilization energy for the [(‐Ala‐Ala‐Gly‐) 2 ] 3 sequence, known to be disfavored in collagen. The present study proves that by using first principles methods for calculating stabilities of supramolecular complexes, such as collagen and β‐pleated sheets, one can obtain stability data in full agreement with experimental observations, which envisage the applicability of QM in molecular design. © 2008 Wiley Periodicals, Inc.J Comput Chem, 2008