3 years ago

Structure and hydrogen bonds of cyclohexapeptide RA-VII by molecular dynamics simulations and quantum chemical calculations

Yukio Hitotsuyanagi, Masako Takasu, Sakiko Mori, Ryota Morikawa, Yoh Noguchi, Koichi Takeya, Takeshi Miyakawa, Satoshi Yokojima, Hironao Yamada

We computationally examined the structure of anti-tumour bicyclic hexapeptide RA-VII. This peptide adopts three conformations (confs.), A, B and C, in dimethyl sulfoxide (DMSO). Although it was experimentally reported that the structure of conf. A is important for anti-tumour activity, the dynamics of confs. A, B and C are not well known. We performed quantum chemical calculations and molecular dynamics (MD) simulations of RA-VII in DMSO. The MD simulations indicated two different local stable structures for conf. C: a structure containing a bent 18-membered ring and another structure containing a rotated peptide bond between Tyr6 and d-Ala1. The root-mean-square fluctuation of the 14-membered ring for conf. A was larger than that for confs. B and C. Ala4 formed intramolecular hydrogen bonds more often in conf. A than in the other conformations. A large number of hydrogen bonds and large structural fluctuations are important for the anti-tumour activity of RA-VII. Our results for the structural change of conf. C and the analysis of the dynamics for confs. A, B and C may contribute to the design of new analogues of cyclic peptides.

Publisher URL: http://www.tandfonline.com/doi/full/10.1080/08927022.2017.1342122

DOI: 10.1080/08927022.2017.1342122

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