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Molecular dynamics simulations of peptides from BPTI: A closer look at amide-aromatic interactions
被引:84
作者:
vanderSpoel, D
vanBuuren, AR
Tieleman, DP
Berendsen, HJC
机构:
[1] UNIV GRONINGEN,BIOSON RES INST,NL-9747 AG GRONINGEN,NETHERLANDS
[2] UNIV GRONINGEN,BIOPHYS CHEM LAB,NL-9747 AG GRONINGEN,NETHERLANDS
关键词:
chemical shift;
molecular dynamics;
bovine pancreatic trypsin inhibitor;
D O I:
10.1007/BF00410322
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Molecular dynamics (MD) simulations of short peptides in water were performed to establish whether it is possible to reproduce experimental data from chemical shift measurements by nuclear magnetic resonance spectroscopy. Three different tetrapeptides were studied. The first, YTGP (Tyr-Thr-Gly-Pro), shows an electrostatic interaction between the aromatic ring of Tyr and the backbone amide hydrogen atom of Gly. The second, YTAP (Tyr-Thr-Ala-Pro), cannot make such an interaction because of steric hindrance of the Ala side chain and hence does not show a well-defined conformation. The third, FTGP (Phe-Thr-Gly-Pro), is shown to alternate between two different conformations. It is demonstrated that small differences in chemical shift, corresponding to these slightly different conformations, can be quantitatively modeled in MD simulations when using the proper force-field parameters and water model. Explicit inclusion of hydrogen atoms on the aromatic rings is essential for a proper description of electrostatic interactions, but the choice of the water model is equally important. We found that a combination of the SPC/E water model and a revised GROMOS87 force field gives close agreement with experiment, while the same and other force fields in combination with SPC or TIP3P water did not reproduce the NMR data at all. Simulations of a longer peptide from bovine pancreatic trypsin inhibitor, containing the YTGP sequence, did show the interaction between the aromatic ring and the amide hydrogen, but not as pronounced as the simulations of shorter peptides.
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页码:229 / 238
页数:10
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