Structural studies of adipokinetic hormones in water and DPC micelle solution using NMR distance restrained molecular dynamics

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• 作者：Graham E. Jackson^a ; ^{Graham.Jackson@uct.ac.za" class="auth_mail} ; Riedaa Gamieldien^a ; Grace Mugumbate^a ; Gerd Gä ; de^b
• 关键词：Adipokinetic hormones (AKHs) ; Melme-CC ; Declu-CC ; Molecular dynamics simulations and receptor docking
• 刊名：Peptides
• 出版年：March, 2014
• 年：2014
• 卷：53
• 期：Complete
• 页码：270-277
• 全文大小：2060 K

文摘

Melme-CC (pGlu-Leu-Asn-Tyr-Ser-Pro-Asp-Trp amide) and Declu-CC (pGlu-Leu-Asn-Phe-Ser-Pro-Asn-Trp-Gly-Asn amide) are members of the insect adipokinetic hormone family with very different activities in the locust bioassay. The conformations of both peptides were determined in water and in a phospholipid (DPC) micelle solution using nuclear magnetic resonance (NMR) restrained molecular dynamics simulations.

In water, Melme-CC has one dominant conformation while in DPC solution it has two preferred conformation. In water, Declu-CC has two conformations but in DPC solution it has one preferred conformation, which is similar to one of the water conformations. All the conformations have type IV 尾-turn between residues 4 and 7.

The binding of the two peptides to the DPC micelle is different. Melme-CC does not bind strongly to the surface and is oriented with the 尾-turn facing the surface. Declu-CC interacts more strongly with the 尾-turn facing away from the surface. Both termini having hydrophobic interactions with the surface. In Declu-CC the side chain of Asn⁷ projects away from the chain while in Melme-CC the Asp⁷ side chain is folded inside the chain. The different orientation of these side chains may account for the much higher biological activity of Declu-CC in mobilizing lipids in the locust compared to the poor biological effect of Melme-CC in this bioassay. Receptor binding of Declu-CC was tested using a model AKH receptor from Anopheles gambiae. A free energy of binding of 鈭?8.5 kJ mol^鈭? was found.