[Study of conformational mobility of insulin, proinsulin, and insulin-like growth factors]

In this work, by method of molecular dynamics there was performed comparative analysis of conformational mobility of evolutionary related peptides--insulin, proinsulin, IGF1, and IGF2. The highest mobility has been shown to be characteristic of the proinsulin molecule, while the lower mobility--IGF1 and proinsulin. The rotation radius (Rg) of insulin, IGF1, and IGF2 changes insignificantly. The proinsulin Rg decreases with leaving to plateau after 6000 ps. Graphs of the mean square deviations (RMSD) from initial positions for A- and B-domains are practically identical, which indicates integrity of the carcass formed by A- and B-domains. The proinsulin C-domain behaves sufficiently chaotically. The IGF1 and IGF2 C-domains form the ordered structures reminding horseshoe and elongated hairpin. The particularly major contribution to the IGF2 mobility is made by D-domain by remaining practically immobile in IGF1, which can be the cause of the high stability of IGF1. The obtained data can be used at development of novel effective drugs for treatment of diabetes mellitus, based on principle of evolutionary relationship of peptides.