The purpose of the work was to investigate at the molecular structural and energy levels the consequence of amino acid substitutions in collagen that cause systemic diseases. The data have been systematized on defects in human collagen 111, and the patterns of single-nucleotide polyrnorphisms collected. Then molecular mechanics calculations were performed for native and mutant collagen molecule fragments. The observed energy components and structural alterations that accompany particular amino acid substitutions were used to propose an interpretation of negative consequences in terms of stability and hydration of the macromolecule.
This paper concerns the conformational variability of collagen as related to the concrete tripeptides (GXY)n constituting its primary structure. The previously elaborated model (V.G.Tumanyan, N.G.Esipova, Biophysics 28, 1021-1025, 1983) with two nets of hydrogen bonds is useful for tripeptides where X is an amino acid. If X is an imino acid, the common one-bonded Rich & Crick model is valid. In this work, compound sequences including tripeptides of different types are considered. Molecular mechanics is used to assess the conformations of the junction regions when a structure with two nets of hydrogen bonds precedes the structure with one net, and vice versa. Thus, all types of sequences typical for natural collagen are covered. It is shown that the combined model representing an alternation of the two-H-bonded model and the one-H-bonded Rich & Crick model is satisfactory stereochemically, and provides more favorable energy in comparison with the continuous one-H-bonded model. Besides, a more favorable hydration of the molecule occures in this case. Some conclusions are made about interchain and intrachain ionic bonds. Thus, it is deduced for the concrete fibrillar protein how a one-dimensional structure determines three-dimensional structure. The macromolecular structure thus suggested is in accord with the experimental data on hydrogen exchange.
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