MOLECULAR-DYNAMICS SIMULATIONS OF PEPTIDES FROM BPTI - A CLOSER LOOK AT AMIDE-AROMATIC INTERACTIONS

Molecular dynamics (MD) simulations of short peptides in water were pe rformed to establish whether it is possible to reproduce experimental data from chemical shift measurements by nuclear magnetic resonance sp ectroscopy. Three different tetrapeptides were studied. The first, YTG P (Tyr-Thr-Gly-Pro), shows an electrostatic interaction between the ar omatic ring of Tyr and the backbone amide hydrogen atom of Gly. The se cond, 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 we ll-defined conformation. The third, FTGP (Phe-Thr-Gly-Pro), is shown t o alternate between two different conformations. It is demonstrated th at small differences in chemical shift, corresponding to these slightl y different conformations, can be quantitatively modeled in MD simulat ions when using the proper force-field parameters and water model. Exp licit inclusion of hydrogen atoms on the aromatic rings is essential f or a proper description of electrostatic interactions, but the choice of the water model is equally important. We found that a combination o f the SPC/E water model and a revised GROMOS87 force field gives close agreement with experiment, while the same and other force fields in c ombination with SPC or TIP3P water did not reproduce the NMR data at a ll. Simulations of a longer peptide from bovine pancreatic trypsin inh ibitor, containing the YTGP sequence, did show the interaction between the aromatic ring and the amide hydrogen, but not as pronounced as th e simulations of shorter peptides.