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J Phys Chem B. 2009 Jul 2;113(26):8983-92. doi: 10.1021/jp808690m.

Molecular dynamics investigations on the effect of D amino acid substitution in a triple-helix structure and the stability of collagen.

Author information

1
Chemical Laboratory, Central Leather Research Institute, Council of Scientific Industrial Research, Sardar Patel Road, Adyar, Chennai 600 020, India.

Abstract

Studies on the structure and stability of peptides and proteins during l-->d configurational change are certainly important for the designing of peptides with new biological activity and protein engineering. The l-->d amino acid (d AA) changes have been observed in aged proteins such as collagen. Hence, in this study, an attempt has been made to explore the effect of the replacement of l amino acid (l AA) in the model collagen-like peptides with d AA and the origin of structural stability (destability) has been traced using the molecular dynamics (MD) method employing the AMBER force field. Our results reveal that the substitution of d AA produces a large local disruption to the triple-helical structure. Formation of a kink (bulge) at the site of substitution is observed from the detailed analysis of MD trajectory. However, this local perturbation of kinked helix changes the direction of the helices and affects the relative orientation of the respective AA residues for helix-helix interaction, enough to affect the overall stability of the model collagen-like peptide. The destabilization energy per d Ala substitution is 7.87 kcal/mol, which is similar to the value for the Gly-->Ala mutation in collagen. Since the Gly-->Ala mutation is involved in genetic disorders such as osteogenesis imperfecta (OI), the l-->d configurational change may produce a similar effect on collagen.

PMID:
19518060
DOI:
10.1021/jp808690m
[Indexed for MEDLINE]

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