Cyclosporin A: Conformational Complexity and Chameleonicity.
Cyclosporin A: Conformational Complexity and Chameleonicity.
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DOI：
10.1021/acs.jcim.1c00771
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发表时间：
2021-11-22
影响因子：
5.6
通讯作者：
Lokey, R. Scott
中科院分区：
文献类型：
--
作者：
Ono, Satoshi;Naylor, Matthew R.;Townsend, Chad E.;Okumura, Chieko;Okada, Okimasa;Lee, Hsiau-Wei;Lokey, R. Scott
The chameleonic behavior of cyclosporin A (CsA) was investigated through conformational ensembles employing multicanonical molecular dynamics simulations that could sample the cis and trans isomers of N-methylated amino acids; these assessments were conducted in explicit water, dimethyl sulfoxide, acetonitrile, methanol, chloroform, cyclohexane (CHX), and n-hexane (HEX) using AMBER ff03, AMBER10:EHT, AMBER12:EHT, and AMBER14:EHT force fields. The conformational details were discussed employing the free-energy landscapes (FELs) at T = 300 K; it was observed that the experimentally determined structures of CsA were only a part of the conformational space. Comparing the ROESY measurements in CHX-d12 and HEX-d14, the major conformations in those apolar solvents were essentially the same as that in CDCl3 except for the observation of some sidechain rotamers. The effects of the metal ions on the conformations, including the cis/trans isomerization, were also investigated. Based on the analysis of FELs, it was concluded that the AMBER ff03 force field best described the experimentally derived conformations, indicating that CsA intrinsically formed membrane-permeable conformations and that the metal ions might be key to the cis/trans isomerization of N-methylated amino acid before binding a partner protein.
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影响因子：
8.3
作者：
Czogalla A
通讯作者：
Czogalla A
影响因子：
2.9
作者：
FEJZO, J;ETZKORN, FA;WAGNER, G
通讯作者：
WAGNER, G
影响因子：
56.9
作者：
ALTSCHUH, D;VIX, O;THIERRY, JC
通讯作者：
THIERRY, JC
影响因子：
3
作者：
Duan, Y;Wu, C;Kollman, P
通讯作者：
Kollman, P
DOI：
10.1039/c0cp00111b
发表时间：
2010-07-28
期刊：
Physical chemistry chemical physics : PCCP
影响因子：
--
作者：
Dupradeau FY;Pigache A;Zaffran T;Savineau C;Lelong R;Grivel N;Lelong D;Rosanski W;Cieplak P
通讯作者：
Cieplak P