Structure and hydrogen bonds of cyclohexapeptide RA-VII by molecular dynamics simulations and quantum chemical calculations. Issue 1 (2nd January 2018)

• Record Type: Journal Article
• Authors: Noguchi, Yoh; Yamada, Hironao; Mori, Sakiko; Miyakawa, Takeshi; Morikawa, Ryota; Yokojima, Satoshi; Hitotsuyanagi, Yukio; Takeya, Koichi; Takasu, Masako
• Is Part Of: Molecular simulation. Volume 44:Issue 1(2018)
• Page Start: 73
• Page End: 84
• Publication Date: 2018-01-02
• Subjects: Molecular dynamics simulation -- quantum chemical calculation -- cyclic peptide -- hydrogen bond -- anti-tumour activity; Molecular dynamics -- Computer simulation -- Periodicals; Statistical mechanics -- Computer simulation -- Periodicals; 539.6
• DOI: 10.1080/08927022.2017.1342122
• Languages: English
• ISSNs: 0892-7022

Abstract

Abstract: 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 Tyr 6 andd -Ala 1 . The root-mean-square fluctuation of the 14-membered ring for conf. A was larger than that for confs. B and C. Ala 4 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.