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The severity of osteogenesis imperfecta: A comparison to the relative free energy differences of collagen model peptides
Author(s) -
Lee KyungHoon,
Kuczera Krzysztof,
Banaszak Holl Mark M.
Publication year - 2011
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21552
Subject(s) - chemistry , mutant , peptide , intramolecular force , osteogenesis imperfecta , residue (chemistry) , crystallography , disulfide bond , molecular dynamics , wild type , stereochemistry , computational chemistry , biochemistry , gene , medicine , pathology
Molecular dynamics simulations were carried out to calculate free energy differences between the folded and unfolded states of wild type and mutant collagen model peptides. The calculated stability of the collagen models was compared with the severity of osteogenesis imperfecta. Free energy differences of Gly → Xaa (Xaa: Ser, Cys, Glu, and Asp) mutations between the wild type and the mutants at position 15 of the model peptide were 3.8, 4.2, 5.6, and 8.8 kcal/mol, respectively. The corresponding free energy differences of a second Gly mutation at the same position in different chains were, on average, 1.3, 1.5, 2.9, and 5.4 kcal/mol, respectively. Free energy simulations were also performed to estimate the relative stability between an oxidized form and a reduced form of the mutants containing two Cys residues, which indicated that the mutant of the collagen‐like peptide containing an intramolecular disulfide bond was more stable than the mutant containing one Cys residue but less stable than the wild type. The calculated free energy differences between an oxidized and a reduced form of the mutants containing two Cys residues are 0.8 and 2.6 kcal/mol for the disulfide bonds between Chains A and B and between Chains A and C, respectively. © 2010 Wiley Periodicals, Inc. Biopolymers 95: 182–193, 2011.