Graharn A. Worth
Theoretische Chemie, Physikalisch-Chemisches Institut, Universitt
Heidelberg, INF 253,
69120 Heidelberg, Germany
Frederico Nardi and Rebecca C. Wade
European Molecalar Biology Laboratory, Meyerhoistrasse 1, 69012
Heidelberg, Germany
Abstract
NMR studies of the YTGP tetrapeptide in aqueous solution show a large structural shift on the g]ycine peptideproton, indicating that the peptide adopts structures in which the aromatic ring lies close to this proton in an aromatic (i+2) amine interaction (Kemmink and Creighton, J. Mol. Biol. 1993. 234, 86]). Here, molecular dynamics simulations are used to obtain details at the atomic level of the structural properties of this system.To maximize the volume of conformational space searched, 13 separate trajectones of 300 ps were calculated at 300 K, with starting structures chosen from a conformational search, protein crystal structures, and modeling. Analysis shows that together the trajectories sample all the important regions of conformational space. Structures from the trajectories were clustered into conformational states, defined as regions in coordinatespace around maxima in the probability distribution. Nine conformational states with significant populations were identified in which the glycine peptide proton has a large structural NMR shift. The relative importance of the trajectories for the system were assigned using energetic weighting factors, and the four most important trajectories were then extended to 1 ns. The structural shift spectra calculated from the significantly populated conformational states with an aromatic (i+2) amine interaction are in good agreement with the experimental spectrum. The analysis shows that the potential energy surface of the system is complicated and divided into two separate regions at this temperature.
J. Phys. Chem. (1998) 32, 6260-6272.